Locomotor activity is a measure of

animal behavior Ethology is a branch of zoology that studies the behaviour of non-human animals. It has its scientific roots in the work of Charles Darwin and of American and German ornithologists of the late 19th and early 20th century, including Charle ...

which is employed in

scientific research The scientific method is an empirical method for acquiring knowledge that has been referred to while doing science since at least the 17th century. Historically, it was developed through the centuries from the ancient and medieval world. The ...

. Hyperlocomotion, also known as locomotor hyperactivity, hyperactivity, or increased locomotor activity, is an effect of certain

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

s in animals in which locomotor activity (locomotion) is increased. It is induced by certain drugs like

psychostimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition ...

s and

NMDA receptor antagonist NMDA receptor antagonists are a class of drugs that work to receptor antagonist, antagonize, or inhibit the action of, the NMDA, ''N''-Methyl-D-aspartate receptor (NMDA receptor, NMDAR). They are commonly used as anesthetics for humans and anima ...

s and is reversed by certain other drugs like

antipsychotic Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...

s and certain

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

s. Stimulation of locomotor activity is thought to be mediated by increased signaling in the

nucleus accumbens The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for ' nucleus adjacent to the septum') is a region in the basal forebrain rostral to the preoptic area of the hypo ...

, a major brain area involved in

behavioral activation Behavioral activation (BA) is a third-generation behavior therapy for treating mood disorders. Behavioral activation primarily emphasizes engaging in positive and enjoyable activities to enhance one's mood. The Beck Institute describes BA as a ...

and

motivated behavior Motivation is an internal state that propels individuals to engage in goal-directed behavior. It is often understood as a force that explains why people or animals initiate, continue, or terminate a certain behavior at a particular time. It i ...

. Hypolocomotion, also known as locomotor hypoactivity, hypoactivity, and decreased locomotor activity, is an effect of certain drugs in animals in which locomotor activity is decreased. It is a characteristic effect of many

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, depressants and interact with brain activity, causing its decelera ...

agents and

general anesthetic General anaesthetics (or anesthetics) are often defined as compounds that induce a loss of consciousness in humans or loss of righting reflex in animals. Clinical definitions are also extended to include an induced coma that causes lack of aware ...

Antipsychotic Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...

s, which are

dopamine receptor antagonist A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and have been used in tr ...

s, and many

serotonergic agent A serotonergic substance, medication, or receptor protein is one that affects neurotransmission pathways that involve serotonin, as follows: * Serotonergic drugs ** Serotonin receptor agonists ** Serotonin receptor antagonists ** Serotonin reupta ...

s, such as ''meta''-chlorophenylpiperazine (mCPP), can also produce this effect, often as a

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

. Although locomotor activity is mainly an animal behavior test, it has also been evaluated in humans. People with

attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by symptoms of inattention, hyperactivity, impulsivity, and emotional dysregulation that are excessive and pervasive, impairing in multiple con ...

(ADHD), in the manic phase of

bipolar disorder Bipolar disorder (BD), previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that each last from days to weeks, and in ...

, on acute

amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

, and with

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

show increased locomotor activity, while children with

autism Autism, also known as autism spectrum disorder (ASD), is a neurodevelopmental disorder characterized by differences or difficulties in social communication and interaction, a preference for predictability and routine, sensory processing d ...

show decreased locomotor activity. Conversely, reduced locomotor activity is observed in bipolar individuals on

mood stabilizer A mood stabilizer is a psychiatric medication used to treat mood disorders characterized by intense and sustained mood shifts, such as bipolar disorder and the bipolar type of schizoaffective disorder. Uses Mood stabilizers are best known for t ...

s and may be a characteristic symptom of the inattentive type of ADHD (ADHD-PI) and

sluggish cognitive tempo Cognitive disengagement syndrome (CDS) is a syndrome characterized by developmentally inappropriate, impairing, and persistent levels of decoupled attentional processing from the ongoing external context and resultant hypoactivity. Symptoms oft ...

Drugs affecting locomotor activity

Dopaminergic agents

Dopamine releasing agents

Hyperlocomotion is induced by

dopamine releasing agent A dopamine releasing agent (DRA) is a type of drug which induces the release of dopamine in the Body (biology), body and/or brain. No binding selectivity, selective DRAs are currently known. However, non-selective DRAs, including norepinephrin ...

s (DRAs) and

s like

and

methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...

. These drugs likewise induce stereotypies.

Dopamine reuptake inhibitors

The

dopamine reuptake inhibitor A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dop ...

s (DRIs)

amineptine Amineptine, formerly sold under the brand name Survector among others, is an atypical antidepressant of the tricyclic antidepressant (TCA) family. It acts as a selective and mixed dopamine reuptake inhibitor and releasing agent, and to a le ...

bupropion Bupropion, formerly called amfebutamone, and sold under the brand name Wellbutrin among others, is an atypical antidepressant that is indicated in the treatment of major depressive disorder, seasonal affective disorder, and to support smo ...

, and

nomifensine Nomifensine, formerly sold under the brand names Merital and Alival, is a norepinephrine–dopamine reuptake inhibitor (NDRI) drug that was developed in the 1960s by Hoechst AG (now Sanofi-Aventis), who then test marketed it in the United States ...

increase spontaneous locomotor activity in animals. The DRI

cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

increases locomotor activity similarly to the preceding DRIs and to

s. The atypical DRI

modafinil Modafinil, sold under the brand name Provigil among others, is a central nervous system (CNS) stimulant and wakefulness-promoting agent, eugeroic (wakefulness promoter) medication used primarily to treat narcolepsy, a sleep disorder characteri ...

does not produce hyperlocomotion in animals.

Dopamine receptor agonists

Direct

dopamine receptor agonist A dopamine agonist is a compound that activates dopamine receptors. There are two families of dopamine receptors, D1-like and D2-like. They are all G protein-coupled receptors. D1- and D5-receptors belong to the D1-like family and the D2-like ...

s like

apomorphine Apomorphine, sold under the brand name Apokyn among others, is a type of aporphine having activity as a non- selective dopamine agonist which activates both D2-like and, to a much lesser extent, D1-like receptors. It also acts as an antago ...

show biphasic effects, decreasing locomotor activity at low doses and increasing locomotor activity at high doses.

Dopamine receptor antagonists

Drug-induced hyperlocomotion can be reversed by various drugs, such as

s acting as

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

D₂ receptor

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain. Reversal of drug-induced hyperlocomotion has been used as an animal test of drug antipsychotic-like activity. Reversal of amphetamine- and NMDA receptor antagonist-induced stereotypies is also employed as a test of drug antipsychotic-like activity.

Adrenergic agents

Norepinephrine releasing agents

Selective

norepinephrine releasing agent A norepinephrine releasing agent (NRA), also known as an adrenergic releasing agent, is a catecholaminergic type of drug that induces the release of norepinephrine (noradrenaline) and epinephrine (adrenaline) from the pre-synaptic neuron into ...

s (NRAs) include

ephedrine Ephedrine is a central nervous system (CNS) stimulant and sympathomimetic agent that is often used to prevent hypotension, low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred ...

pseudoephedrine Pseudoephedrine, sold under the brand name Sudafed among others, is a sympathomimetic medication which is used as a decongestant to treat nasal congestion. It has also been used off-label for certain other indications, like treatment of lo ...

phenylpropanolamine Phenylpropanolamine (PPA), sold under many brand names, is a sympathomimetic agent used as a decongestant and appetite suppressant. It was once common in prescription and over-the-counter cough and cold preparations. The medication is taken ...

levomethamphetamine Levomethamphetamine (International Nonproprietary Name, INN: levmetamfetamine) is an optical isomer of methamphetamine primarily used as a Topical decongestant, topical nasal decongestant. Levomethamphetamine is used to treat nasal congestion f ...

, and D-phenylalaninol. However, these drugs also release

to a much lesser extent (e.g., ~10-fold less potently). Ephedrine consistently stimulates locomotor activity in rodents. However, the hyperlocomotion induced by ephedrine may be mediated by dopamine release rather than by norepinephrine release. On the other hand, lesioning the brain noradrenergic system with the noradrenergic neurotoxin DSP-4 reduces

dextroamphetamine Dextroamphetamine (international nonproprietary name, INN: dexamfetamine) is a potent central nervous system (CNS) stimulant and enantiomer of amphetamine that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narc ...

-induced hyperlocomotion. In addition, the selective α₁-adrenergic receptor antagonist

prazosin Prazosin, sold under the brand name Minipress among others, is a medication used to treat high blood pressure, symptoms of an enlarged prostate, and nightmares related to post-traumatic stress disorder (PTSD). It is an α1 blocker. It is a les ...

antagonizes amphetamine-induced hyperlocomotion and

knockout A knockout (abbreviated to KO or K.O.) is a fight-ending, winning criterion in several full-contact combat sports, such as boxing, kickboxing, Muay Thai, mixed martial arts, karate, some forms of taekwondo and other sports involving striking, ...

of the α_1B-adrenergic receptor dramatically reduces dextroamphetamine-induced hyperlocomotion. In contrast to ephedrine and

, pseudoephedrine and phenylpropanolamine do not stimulate locomotor activity in rodents. However, in another study, pseudoephedrine was able to increase locomotor activity. A potential

confounding factor In causal inference, a confounder is a variable that influences both the dependent variable and independent variable, causing a spurious association. Confounding is a causal concept, and as such, cannot be described in terms of correlati ...

with

β-hydroxyamphetamine Hydroxyamphetamine may refer to: * β-Hydroxyamphetamine (phenylisopropanolamine; two chiral centers and four possible stereoisomers) ** Phenylpropanolamine (racemic phenylpropanolamine; norephedrine; (1''R'',2''S''/1''S'',2''R'')-β-hydroxyampheta ...

s like phenylpropanolamine, ephedrine, and pseudoephedrine is that they have lower

lipophilicity Lipophilicity (from Greek λίπος "fat" and φίλος "friendly") is the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such compounds are called lipophilic (translated ...

compared to their amphetamine counterparts, with consequent reduced capacity to cross the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

and produce

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

effects. Conversely, the potencies of

monoamine releasing agent A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of one or more monoamine neurotransmitters from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrati ...

s (MRAs) in producing amphetamine-type subjective effects in humans have been found to correlate with their potency to induce norepinephrine release and not with their potencies to induce dopamine release. In addition,

self-administration Self-administration is, in its Medicine, medical sense, the process of a subject administering a Pharmacology, pharmacological substance to themself. A clinical example of this is the subcutaneous "self-injection" of insulin by a Diabetes, diabetic ...

appeared to be relatively resistant to blockade by

s. Findings on the modulation of the

ventral tegmental area The ventral tegmental area (VTA) (tegmentum is Latin for ''covering''), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is th ...

by the noradrenergic

locus coeruleus The locus coeruleus () (LC), also spelled locus caeruleus or locus ceruleus, is a nucleus in the pons of the brainstem involved with physiological responses to stress and panic. It is a part of the reticular activating system in the reticular ...

are mixed and suggestive of both excitatory and inhibitory roles. The α₁-adrenergic receptor appears to be facilitatory, whereas the α₂-adrenergic receptor appears to be inhibitory, and the

β-adrenergic receptor The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like bet ...

s appear to not be involved. More research is needed to investigate the role of norepinephrine in dopamine modulation and stimulant-like effects. In contrast to normal mice, psychostimulants like amphetamine,

β-phenethylamine Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace ami ...

, and

methylphenidate Methylphenidate, sold under the brand names Ritalin ( ) and Concerta ( ) among others, is a central nervous system (CNS) stimulant used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It may be taken Oral adm ...

lose their ability to elevate brain dopamine but not norepinephrine in

dopamine transporter The dopamine transporter (DAT, also sodium-dependent dopamine transporter) is a membrane-spanning protein coded for in humans by the ''SLC6A3'' gene (also known as ''DAT1''), that pumps the neurotransmitter dopamine out of the synaptic cleft ba ...

(DAT)

knockout mice A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or " knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...

and have been found to decrease locomotor activity in these mice. Paradoxically however,

retains reinforcing effects in DAT knockout mice and cocaine and amphetamine are still able to elevate dopamine in the medial nucleus accumbens in these mice. It was found that the

norepinephrine reuptake inhibitor A norepinephrine reuptake inhibitor (NRI, NERI) or noradrenaline reuptake inhibitor or adrenergic reuptake inhibitor (ARI), is a type of drug that acts as a reuptake inhibitor for the neurotransmitters norepinephrine (noradrenaline) and epinep ...

reboxetine Reboxetine, sold under the brand name Edronax among others, is a selective norepinephrine reuptake inhibitor (sNRI) medication marketed as an antidepressant by Pfizer for use in the treatment of major depressive disorder, although it has also be ...

increases dopamine levels in the nucleus accumbens in DAT knockout mice but not in normal mice, suggesting that the effects of norepinephrine elevation change in the brains of DAT knockout mice. Whereas

dextromethamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational or performance-enhancing drug and less commonly as a second-line treatment for attention deficit hyperactivity di ...

is a well-balanced

norepinephrine–dopamine releasing agent A norepinephrine–dopamine releasing agent (NDRA) is a type of drug which induces the synapse, release of norepinephrine (and epinephrine) and dopamine in the body and/or brain. Many of these are amphetamine type stimulants. Examples Examples ...

(NDRA), levomethamphetamine is a selective NRA. Levomethamphetamine has similar potency as an NRA compared to dextromethamphetamine. Conversely, levomethamphetamine is about 15- to 20-fold less potent in inducing dopamine release than dextromethamphetamine. In accordance with the preceding, levomethamphetamine was found to selectively induce brain norepinephrine release with minimal effect on brain dopamine release across an assessed dosage range in rodents. The drug did not increase locomotor activity at the assessed doses, in which brain dopamine release was not affected. In contrast to levomethamphetamine, dextromethamphetamine at the same doses increased brain levels of both norepinephrine and dopamine and induced dose-dependent hyperlocomotion. Relatedly, levomethamphetamine shows similar sympathomimetic effects as dextromethamphetamine but is substantially less potent as a

in animals. As in rodents, levomethamphetamine showed reduced reinforcing and stimulant-like effects compared to dextromethamphetamine in

rhesus monkey The rhesus macaque (''Macaca mulatta''), colloquially rhesus monkey, is a species of Old World monkey. There are between six and nine recognised subspecies split between two groups, the Chinese-derived and the Indian-derived. Generally brown or g ...

Animal studies Animal studies is a recently recognised field in which animals are studied in a variety of cross-disciplinary ways. Scholars who engage in animal studies may be formally trained in a number of diverse fields, including art history, anthropology ...

of the reinforcing and

-like effects of

s (DRAs) with varying capacities to release norepinephrine and

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

in rodents and monkeys have suggested that in contrast to the case of serotonin release, which inhibits the reinforcing and stimulant-like effects of these agents, norepinephrine release has minimal influence on their misuse liability and associated effects.

Norepinephrine reuptake inhibitors

Norepinephrine reuptake inhibitor A norepinephrine reuptake inhibitor (NRI, NERI) or noradrenaline reuptake inhibitor or adrenergic reuptake inhibitor (ARI), is a type of drug that acts as a reuptake inhibitor for the neurotransmitters norepinephrine (noradrenaline) and epinep ...

s (NRIs), like

atomoxetine Atomoxetine, formerly sold under the brand name Strattera, is a selective norepinephrine reuptake inhibitor (sNRI) medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, cognitive disengagement syndr ...

, and desipramine, do not increase locomotor activity in rodents and instead show no effect on locomotor activity or decrease it. In addition, NRIs decrease

-, and

phencyclidine Phencyclidine or phenylcyclohexyl piperidine (PCP), also known in its use as a street drug as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hall ...

(PCP)-induced hyperlocomotion in rodents. Accordingly, atomoxetine has been reported to attenuate the stimulant and rewarding effects of

in humans. A variety of different NRIs were shown to decrease spontaneous locomotor activity in a novel environment when given acutely and to decrease locomotor activity in both novel and familiar environments when given chronically in rodents. Similarly,

norepinephrine transporter The norepinephrine transporter (NET), also known as noradrenaline transporter (NAT), is a protein that in humans is encoded by the solute carrier family 6 member 2 (SLC6A2) gene. NET is a monoamine transporter and is responsible for the sodium ...

(NET)

had low basal locomotor activity. However, combination of an NRI with dopamine reuptake inhibition resulted in increased locomotor activity. It was concluded that norepinephrine reuptake inhibition by itself decreases locomotor activity unless it is combined with dopamine reuptake inhibition.

Serotonergic agents

Serotonin releasing agents

Certain

serotonin releasing agent A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter ...

s (SRAs), like

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy (tablet form), and molly (crystal form), is an empathogen–entactogenic drug with stimulant and minor Psychedelic drug, psychedelic properties. In studies, it has been used ...

and

MDAI MDAI, also known as 5,6-methylenedioxy-2-aminoindane, is an entactogen drug of the 2-aminoindane group which is related to MDMA and produces similar subjective effects. It acts as a selective serotonin and norepinephrine releasing agent (SNR ...

, though notably not others, like

chlorphentermine Chlorphentermine, sold under the brand names Apsedon, Desopimon, and Lucofen, is a serotonergic appetite suppressant of the amphetamine family. Developed in 1962, it is the ''para''- chloro derivative of the better-known appetite suppressant ph ...

fenfluramine Fenfluramine, sold under the brand name Fintepla, is a serotonergic medication used for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome. It was formerly used as an appetite suppressant in the treat ...

, and MMAI, induce locomotor hyperactivity in animals. This is dependent on serotonin release allowed for by the

serotonin transporter The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene. SERT is a type of monoamine transporter protein t ...

(SERT) and serotonin 5-HT_2B receptor. SERT

, pretreatment with

serotonin reuptake inhibitor A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) by blocking the drug action, action of the serotonin transporter (SERT). This in turn lea ...

s (SRIs) (which block MDMA-induced SERT-mediated serotonin release), or serotonin 5-HT_2B receptor knockout (which likewise blocks MDMA-induced serotonin release), all completely block MDMA-induced locomotor hyperactivity. In addition, locomotor hyperactivity produced by MDMA is partially attenuated by serotonin 5-HT_1B receptor antagonism (or

) or by serotonin 5-HT_2A receptor antagonism. The locomotor hyperactivity produced by MDMA is fully attenuated by combined serotonin 5-HT_1B and 5-HT_2A receptor antagonism. Conversely, the serotonin 5-HT_1A receptor is not involved in MDMA-induced hyperlocomotion. Serotonin 5-HT_2C receptor activation appears to inhibit MDMA-induced hyperlocomotion, and antagonism of this receptor has been reported to markedly enhance the locomotor hyperactivity induced by MDMA. Activation of the serotonin 5-HT_2C receptor is known to inhibit dopamine release in the

mesolimbic pathway The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmental area in the midbrain to the ventral striatum of the basal ganglia in the forebrain. The v ...

as well as to inhibit dopamine release in the nigrostriatal and

mesocortical pathway The mesocortical pathway is a dopaminergic pathway that connects the ventral tegmentum to the prefrontal cortex. It is one of the four major dopamine pathways in the brain. It is essential to the normal cognitive function of the dorsolateral pre ...

s. Although the serotonin system has been implicated in the hyperlocomotion of SRAs, certain SRAs, such as MDMA, are actually

serotonin–norepinephrine–dopamine releasing agent A serotonin–norepinephrine–dopamine releasing agent (SNDRA), also known as a triple releasing agent (TRA), is a type of drug which induces the release of serotonin, norepinephrine/epinephrine, and dopamine in the brain and body. SNDRAs produc ...

s (SNDRAs), and

catecholamine A catecholamine (; abbreviated CA), most typically a 3,4-dihydroxyphenethylamine, is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. Cate ...

rgic mechanisms are likely to additionally be involved. Relatedly, the α₁-adrenergic receptor antagonist

completely blocks MDMA-induced hyperlocomotion in animals. In addition, the α₁-adrenergic receptor antagonists prazosin and

doxazosin Doxazosin, sold under the brand name Cardura among others, is a medication used to treat symptoms of benign prostatic hyperplasia (enlarged prostate), hypertension (high blood pressure), and post-traumatic stress disorder (PTSD). For high bloo ...

reduce the

and/or

euphoric Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and danci ...

effects of MDMA in humans. Similarly, the

(NRI)

, which prevents MDMA from inducing norepinephrine release, likewise reduces the stimulant effects and emotional excitation of MDMA in humans.

Dopamine receptor Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through diff ...

s also appear to be involved in MDMA-induced hyperlocomotion, although findings in this area, both in animals and humans, seem to be conflicting. In contrast to non-selective SRAs like MDMA, the highly selective SRA MMAI induces hypolocomotion in animals. Similarly, the highly selective SRA chlorphentermine is said to weakly stimulate locomotor activity at low doses and to progressively suppress locomotor activity at higher doses. The reasons for the differences in locomotor activity with different SRAs are not fully clear. In any case, they may be related to factors such as whether the agents are selective SRAs, whether they additionally act as agonists of serotonin 5-HT₂ receptors, and whether they additionally induce the release of norepinephrine and/or dopamine.

Serotonin reuptake inhibitors

Selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs primarily work by blo ...

s (SSRIs) have been reported to have no effect or to increase locomotor activity, at least under certain circumstances like novel environments. However, in other studies, SSRIs have been reported to produce hypolocomotion, an effect that could be reversed by the serotonin 5-HT_2C receptor

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.SB-242084. In another study, the SSRIs

fluoxetine Fluoxetine, sold under the brand name Prozac, among others, is an Antidepressant, antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used for the treatment of major depressive disorder, Anxiety disorder, anx ...

and

citalopram Citalopram, sold under the brand name Celexa among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive compulsive disorder, panic disorder, and soci ...

had no effect on locomotor activity alone or in combination with SB-242084. Fluoxetine has been found to not affect

-induced hyperlocomotion. Similarly,

sertraline Sertraline, sold under the brand name Zoloft among others, is an Antidepressant, antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used to treat major depressive disorder, generalized anxiety disorder, socia ...

did not affect

-induced hyperlocomotion.

Serotonin precursors

The serotonin precursor

5-hydroxytryptophan 5-Hydroxytryptophan (5-HTP), used medically as oxitriptan, is a naturally occurring amino acid and chemical precursor as well as a metabolic intermediate in the biosynthesis of the neurotransmitter serotonin. 5-HTP can be manufactured and use ...

(5-HTP) combined with

benserazide Benserazide is a peripherally acting aromatic L-amino acid decarboxylase or DOPA decarboxylase inhibitor, which is unable to cross the blood–brain barrier. It is on the World Health Organization's List of Essential Medicines. Medical use ...

can suppress the hyperlocomotion induced by

in rodents.

Serotonin receptor agonists

The non-selective

serotonin receptor agonist A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin (5-hydroxytryptamine; 5-HT), a neurotransmitter and hormone and the endogenous ligand of t ...

s and

serotonergic psychedelic Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluci ...

LSD Lysergic acid diethylamide, commonly known as LSD (from German ; often referred to as acid or lucy), is a semisynthetic, hallucinogenic compound derived from ergot, known for its powerful psychological effects and serotonergic activity. I ...

and DOI decrease locomotor activity in animals. However, whereas LSD suppresses locomotion at all doses tested, DOI as well as DOM show an inverted U-shaped dose–response curve, with stimulation of locomotor activity at low doses and suppression of locomotion at higher doses. The hyperlocomotion of DOI at low doses is abolished in

5-HT_2A receptor

, whereas the hypolocomotion with DOI at higher doses is blocked by the selective serotonin 5-HT_2C receptor antagonist SER-082. Similarly, the hyperlocomotion of low doses of DOM is reduced by the serotonin 5-HT_2A receptor antagonist volinanserin (MDL-100907) and enhanced by the serotonin 5-HT_2C receptor antagonist SB-242084 and its hypolocomotion at high doses is attenuated by SB-242084. As such, it has been concluded that serotonin 5-HT_2A receptor activation increases locomotor activity while serotonin 5-HT_2C receptor agonism decreases locomotor activity. The locomotor effects of many other serotonergic psychedelics have also been studied and have often been similar to the preceding agents. However, in other cases, they have been different. The

tryptamine Tryptamine is an indolamine metabolite of the essential amino acid tryptophan. The chemical structure is defined by an indole—a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the firs ...

psychedelics

psilocin Psilocin, also known as 4-hydroxy-''N'',''N''-dimethyltryptamine (4-HO-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic. It is present in most psychedelic mushrooms together with its phosphorylated counterpart psilocy ...

and

5-MeO-DMT 5-MeO-DMT (5-methoxy-''N'',''N''-dimethyltryptamine), also known as ''O''-methylbufotenin or mebufotenin (), is a naturally occurring psychedelic of the tryptamine family. It is found in a wide variety of plant species, and is also secreted by ...

produce profound hypolocomotion in mice and this is blocked by the serotonin 5-HT_1A receptor antagonist

WAY-100635 WAY-100635 is a piperazine drug and research chemical widely used in scientific studies. It was originally believed to act as a selective 5-HT1A receptor antagonist, but subsequent research showed that it also acts as potent full agonist at the ...

or by serotonin 5-HT_1A receptor

but not by the serotonin 5-HT_2C receptor antagonist SB-242084.

5-MeO-DALT 5-MeO-DALT, also known as ''N'',''N''-diallyl-5-methoxytryptamine, or as foxtrot, is a psychedelic drug of the substituted tryptamine, tryptamine and substituted 5-methoxytryptamine, 5-methoxytryptamine families. It was first chemical synthesis, ...

dose-dependently increased locomotor activity but produced a sharp decrease at the highest tested dose. The relatively selective serotonin 5-HT_2A receptor agonist

25I-NBOMe 25I-NBOMe, also known as 2C-I-NBOMe, Cimbi-5, and shortened to "25I", is a psychedelic drug of the phenethylamine, 2C, and NBOMe (25-NB) families. Since 2010, it has circulated in the recreational drug scene, often misrepresented as LSD. It is ...

has been found to show similar locomotor effects to

phenylalkylamine Substituted phenethylamines (or simply phenethylamines) are a chemical class of organic compounds that are based upon the phenethylamine structure; the class is composed of all the derivative compounds of phenethylamine which can be formed by ...

psychedelics, increasing locomotor activity at low doses at decreasing it at higher doses. The selective serotonin 5-HT_2A receptor agonist

25CN-NBOH 25CN-NBOH, also known as NBOH-2C-CN, is a compound indirectly derived from the phenethylamine series of hallucinogens, which was discovered in 2014 at the University of Copenhagen. It is a member of the NBOMe family of psychedelic drug, psychedel ...

modestly increased locomotor activity or did not affect it. The non-selective serotonin 5-HT_2C receptor agonists ''meta''-chlorophenylpiperazine (mCPP) and

Ro60-0175 Ro60-0175, also known as (''S'')-5,6-difluoroindolmethylethylamine, is a serotonin receptor agonist of the isotryptamine group developed by Hoffmann–La Roche, which has applications in scientific research. It acts as a potent and selective ...

as well as the selective serotonin 5-HT_2C receptor agonists WAY-161503 and CP-809101 produce hypolocomotion in rodents. In serotonin 5-HT_2C receptor

, on the other hand, mCPP produced hyperlocomotion. In contrast to most serotonin 5-HT_2C receptor agonists, the selective serotonin 5-HT_2C receptor agonist

WAY-163909 WAY-163,909 is a drug which acts as a potent and reasonably selective agonist for the serotonin 5-HT2C receptor. It has antipsychotic-like effects in animal models, and has been used to study the role of the 5-HT2C receptor subtype in the action ...

had no effect on spontaneous locomotor activity. The selective serotonin 5-HT_2C receptor agonists WAY-163909 and CP-809101 have been found to suppress

-induced hyperlocomotion. The non-selective serotonin 5-HT_2C receptor agonist Ro60-0175 has been found to suppress the hyperlocomotion induced by

, and this effect could be blocked by the selective serotonin 5-HT_2C receptor antagonist SB-242084. CP-809101 has been found to decrease locomotor activity and antagonized

(PCP)-induced hyperlocomotion.

Serotonin receptor antagonists

Serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

5-HT_2A receptor

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.volinanserin (MDL-100907) and

ketanserin Ketanserin, sold under the brand name Sufrexal, is an antihypertensive agent which is used to treat arterial hypertension and vasospasm, vasospastic disorders. It is also used in scientific research as an antiserotonergic medication, agent in th ...

counteract the hyperactivity induced by amphetamine, cocaine, and NMDA receptor antagonists like PCP in animals. Less-selective serotonin 5-HT_2A receptor antagonists, like

trazodone Trazodone is an antidepressant medication used to treat major depressive disorder, anxiety disorders, and insomnia. It is a phenylpiperazine compound of the serotonin antagonist and reuptake inhibitor (SARI) class. The medication is taken or ...

, have been found to decrease locomotor and behavioral activity and to inhibit amphetamine-, cocaine-, and PCP-induced hyperactivity in animals similarly. Blockade of the serotonin 5-HT_2A receptor by

atypical antipsychotic The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as tranquilizers and neurol ...

s like

clozapine Clozapine, sold under the brand name Clozaril among others, is a psychiatric medication and was the first atypical antipsychotic to be discovered. It is used primarily to treat people with schizophrenia and schizoaffective disorder who have ...

and

olanzapine Olanzapine, sold under the brand name Zyprexa among others, is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. It is also sometimes used off-label for treatment of chemotherapy-induced nausea and vomitin ...

contributes to the hypolocomotion they produce. In addition to serotonin 5-HT_2A receptor antagonists, serotonin 5-HT_2A receptor

biased agonist Functional selectivity (or agonist trafficking, biased agonism, biased signaling, ligand bias, and differential engagement) is the ligand-dependent selectivity for certain signal transduction pathways relative to a reference ligand (often the end ...

s that selectively activate the

β-arrestin Arrestins (abbreviated Arr) are a small family of proteins important for regulating signal transduction at G protein-coupled receptors. Arrestins were first discovered in the late '80s as a part of a conserved two-step mechanism for regulatin ...

pathway but not the G_q pathway, like 25N-N1-Nap, have been found to antagonize PCP-induced locomotor hyperactivity in rodents. Serotonin 5-HT_2B receptor antagonists by themselves do not appear to affect locomotor activity. However, antagonists of the serotonin 5-HT_2B receptor decrease the locomotor hyperactivity of amphetamine, cocaine, and

(PCP). The selective serotonin 5-HT_2C receptor antagonist SB-242084 has been found to produce modest hyperlocomotion at high doses in rodents. The drug has also been found to produce modest stimulant-like effects in

squirrel monkey Squirrel monkeys are New World monkeys of the genus ''Saimiri''. ''Saimiri'' is the only genus in the subfamily Saimiriinae. The name of the genus is of Tupi origin (''sai-mirím'' or ''çai-mbirín'', with ''sai'' meaning 'monkey' and ''mirím' ...

s. SB-242084 has additionally been found to enhance the hyperlocomotion of

in rodents. Similarly, it has been found to dose-dependently enhance the hyperlocomotion induced by

dexfenfluramine Dexfenfluramine, formerly sold under the brand name Redux, is a Serotonin, serotonergic drug that was used as an appetite suppressant to promote weight loss. It is the d-enantiomer of fenfluramine and is structurally similar to amphetamine, but ...

in rodents. It has also been found to enhance the hyperlocomotion induced by

, and

, to modestly enhance

nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...

- and

morphine Morphine, formerly also called morphia, is an opiate that is found naturally in opium, a dark brown resin produced by drying the latex of opium poppies (''Papaver somniferum''). It is mainly used as an analgesic (pain medication). There are ...

-induced hyperactivity, and to not affect the hyperactivity induced by RU-24969 or

. The serotonin 5-HT_2C receptor antagonist SB-221284 has been found to augment the

dopamine elevations and hyperlocomotion induced by

s like

(PCP) and dizocilpine (MK-801) in rodents.

Glutamatergic agents

NMDA receptor antagonists

Hyperlocomotion is induced by

s and

dissociative Dissociatives, colloquially dissos, are a subclass of hallucinogens that distort perception of sight and sound and produce feelings of detachment – dissociation – from the environment and/or self. Although many kinds of drugs are capable of ...

hallucinogen Hallucinogens, also known as psychedelics, entheogens, or historically as psychotomimetics, are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mo ...

s such as

(PCP),

ketamine Ketamine is a cyclohexanone-derived general anesthetic and NMDA receptor antagonist with analgesic and hallucinogenic properties, used medically for anesthesia, depression, and pain management. Ketamine exists as its S- (esketamine) a ...

, and dizocilpine (MK-801). These drugs likewise induce stereotypies.

Cholinergic agents

Muscarinic acetylcholine receptor antagonists

Non-selective

muscarinic acetylcholine receptor Muscarinic acetylcholine receptors (mAChRs) are acetylcholine receptors that form G protein-coupled receptor, G protein-coupled receptor complexes in the cell membranes of certain neurons and other Cell (biology), cells. They play several role ...

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.antimuscarinic A muscarinic acetylcholine receptor antagonist, also simply known as a muscarinic antagonist or as an antimuscarinic agent, is a type of anticholinergic drug that blocks the activity of the muscarinic acetylcholine receptors (mAChRs). The muscarin ...

s, such as

atropine Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically give ...

hyoscyamine Hyoscyamine (also known as daturine or duboisine) is a naturally occurring tropane alkaloid and plant toxin. It is a secondary metabolite found in certain plants of the family Solanaceae, including Hyoscyamus niger, henbane, Mandragora officina ...

, and

scopolamine Scopolamine, also known as hyoscine, or Devil's Breath, is a medication used to treat motion sickness and postoperative nausea and vomiting. It is also sometimes used before surgery to decrease saliva. When used by injection, effects begin a ...

, produce robust hyperactivity in animals, but also produce

deliriant Deliriants are a subclass of hallucinogen. The term was coined in the early 1980s to distinguish these drugs from psychedelics such as LSD and dissociatives such as ketamine, due to their primary effect of causing delirium, as opposed to th ...

effects such as

amnesia Amnesia is a deficit in memory caused by brain damage or brain diseases,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be temporarily caused by t ...

and

hallucination A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...

s in both animals and humans.

Cannabinoids

Tetrahydrocannabinol Tetrahydrocannabinol (THC) is a cannabinoid found in cannabis. It is the principal psychoactive constituent of ''Cannabis'' and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C21H30O2) de ...

(THC) produces hypolocomotion in rodents.

Cannabidiol Cannabidiol (CBD) is a phytocannabinoid, one of 113 identified cannabinoids in ''Cannabis'', along with tetrahydrocannabinol (THC), and accounts for up to 40% of the plant's extract. Medically, it is an anticonvulsant used to treat multiple f ...

(CBD) does not appear to affect locomotor activity when administered by itself or when added to THC. However, in some studies, CBD augmented THC-induced hypolocomotion.

Opioids

Classical

opioid Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...

s or

μ-opioid receptor The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalins and beta-endorphin, but a low affinity for dynorphins. They are also referred to as μ(''mu'')-opioid peptide (MOP) receptors. The prototypical ...

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

s like

and

fentanyl Fentanyl is a highly potent synthetic piperidine opioid primarily used as an analgesic (pain medication). It is 30 to 50 times more Potency (pharmacology), potent than heroin and 50 to 100 times more potent than morphine. Its primary Medici ...

stimulate locomotor activity in rodents. However, high doses of μ-opioid receptor agonists induce locomotor depression.

δ-Opioid receptor The δ-opioid receptor, also known as delta opioid receptor or simply delta receptor, abbreviated DOR or DOP, is an inhibitory 7-transmembrane G-protein coupled receptor coupled to the G protein Gi alpha subunit, Gi/G0 and has enkephalins as it ...

agonists like AZD-2327 likewise stimulate locomotor activity in rodents.

TAAR1 modulators

The

trace amine-associated receptor 1 Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the ''TAAR1'' gene. TAAR1 is a primarily intracellular amine-activated and G protein-coupled receptor (GPCR) that is p ...

(TAAR1) regulates the

monoaminergic Monoaminergic means "working on monoamine neurotransmitters", which include serotonin, dopamine, norepinephrine, epinephrine, and histamine. A monoaminergic, or monoaminergic drug, is a chemical, which functions to directly modulate the seroton ...

system and is a

biological target A biological target is anything within a living organism to which some other entity (like an endogenous ligand or a drug) is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets ...

for

trace amine Trace amines are an endogenous group of trace amine-associated receptor 1 (TAAR1) agonists – and hence, monoaminergic neuromodulators – that are structurally and metabolically related to classical monoamine neurotransmitters. Compared to ...

s like

and

tyramine Tyramine ( ) (also spelled tyramin), also known under several other names, is a naturally occurring trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent. Notably, it is unable to cross the bl ...

, the

thyronamine Thyronamine refers both to a molecule, and to derivatives of that molecule: a family of decarboxylated and deiodinated metabolites of the thyroid hormones thyroxine (T4) and 3,5,3'-triiodothyronine (T3). Types The group includes: * Thyronamin ...

3-iodothyronamine, and

s like

s. TAAR1

show unchanged basal locomotor activity. However, they show enhanced hyperlocomotion with

, and

, as well as with

. TAAR1 overexpression likewise is associated with unchanged basal locomotor activity. However, overexpression of the TAAR1 results in only weak locomotor stimulation by amphetamine. The TAAR1

full agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agoni ...

s RO5256390, ulotaront (SEP-363856), and LK00764 have been found to suppress locomotion in mice. Conversely, the TAAR1 full agonist RO5166017 and the TAAR1

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...

s RO5073012, RO5203648, and RO5263397 on their own did not affect basal locomotion in rodents. Similarly, the TAAR1 partial agonist RO5263397 did not affect locomotor activity in monkeys. The TAAR1 antagonist EPPTB does not affect basal locomotor activity in rodents. The TAAR1 full agonists RO5166017, RO5256390, and ulotaront all suppress

-induced hyperlocomotion in mice. The TAAR1 partial agonists RO5073012, RO5203648, and RO5263397 suppress locomotor stimulation induced by

. The TAAR1 partial agonist RO5203648 suppressed

-induced hyperlocomotion at the highest assessed dose in rats but did not affect dextroamphetamine-induced hyperactivity in mice. It showed complex effects on

-induced hyperlocomotion in rats, reducing early but potentiating late methamphetamine-induced hyperlocomotion with acute administration and suppressing methamphetamine-induced hyperlocomotion with chronic administration. The dual TAAR1 full agonist and

5-HT₁ receptor

modulator Signal modulation is the process of varying one or more properties of a periodic waveform in electronics and telecommunication for the purpose of transmitting information. The process encodes information in form of the modulation or message ...

ulotaront did not affect dextroamphetamine-induced hyperlocomotion in rats. The TAAR1 weak partial agonist RO5073012 did not affect

-induced hyperlocomotion in mice but substantially restored the locomotor stimulation of amphetamine in mice with TAAR1 overexpression. In an unpublished study, EPPTB was reported to considerably reduce methamphetamine-induced hyperlocomotion in mice chronically exposed to methamphetamine, an effect that was absent in TAAR1 knockout mice. The TAAR1 full agonists RO5166017, RO5256390, ulotaront, and LK00764 and the TAAR1 partial agonists RO5203648 and RO5263397 suppress the hyperlocomotion induced by

s like

(PCP), L-687,414, and dizocilpine (MK-801) in rodents.

Other agents

Many

tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains ...

s (TCAs) do not increase locomotion, and instead often actually show behavioral sedation.

Non-drug stimuli affecting locomotor activity

Light Light, visible light, or visible radiation is electromagnetic radiation that can be visual perception, perceived by the human eye. Visible light spans the visible spectrum and is usually defined as having wavelengths in the range of 400– ...

exposure has been found to increase locomotor activity and exploratory behavior in rodents.

Similar behavioral measures

Other similar behavioral measures include

stereotypy A stereotypy (, ) is a repetitive or ritualistic movement, posture, or utterance. Stereotypies may be simple movements such as body rocking, or complex, such as self-caressing, crossing and uncrossing of legs, and marching in place. They are foun ...

exploratory behavior Curiosity (from Latin , from "careful, diligent, curious", akin to "care") is a quality related to inquisitive thinking, such as exploration, investigation, and learning, evident in humans and other animals. Curiosity helps human development, ...

, climbing behavior, and jumping behavior.

Amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

s, which are

s (DRAs) induce stereotypies in addition to hyperlocomotion. The

induces stereotypy and climbing behavior. The

dopamine precursor Monoamine precursors are precursors of monoamines and monoamine neurotransmitters in the body. The amino acids L-tryptophan and L-5-hydroxytryptophan (5-HTP; oxitriptan) are precursors of serotonin and melatonin, while the amino acids L-phenyl ...

levodopa Levodopa, also known as L-DOPA and sold under many brand names, is a dopaminergic medication which is used in the treatment of Parkinson's disease (PD) and certain other conditions like dopamine-responsive dystonia and restless legs syndrome. ...

(L-DOPA) induces jumping behavior. These effects can all be reversed by

s, which are

References

{{Pharmacology Animal testing techniques Neuroscience of schizophrenia Psychology experiments Schizophrenia research Symptoms and signs of mental disorders

Drugs affecting locomotor activity

Dopaminergic agents

Dopamine releasing agents

Dopamine reuptake inhibitors

Dopamine receptor agonists

Dopamine receptor antagonists

Adrenergic agents

Norepinephrine releasing agents

Norepinephrine reuptake inhibitors

Serotonergic agents

Serotonin releasing agents

Serotonin reuptake inhibitors

Serotonin precursors

Serotonin receptor agonists

Serotonin receptor antagonists

Glutamatergic agents

NMDA receptor antagonists

Cholinergic agents

Muscarinic acetylcholine receptor antagonists

Cannabinoids

Opioids

TAAR1 modulators

Other agents

Non-drug stimuli affecting locomotor activity

Similar behavioral measures

See also

References