Dopamine
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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 by removing a carboxyl group from a molecule of its precursor chemical, L-DOPA, which is synthesized in the brain and kidneys. Dopamine is also synthesized in plants and most animals. In the brain, dopamine functions as a neurotransmitter—a chemical released by neurons (nerve cells) to send signals to other nerve cells. The brain includes several distinct dopamine pathways, one of which plays a major role in the motivational component of reward-motivated behavior. The anticipation of most types of rewards increases the level of dopamine in the brain, and many addictive drugs increase dopamine release or block its reuptake into neurons following release. Other brain dopamine pathways are involved in motor control and in controllin ...
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Dopamine Receptor D1
Dopamine receptor D1, also known as DRD1. It is one of the two types of D1-like receptor family receptors D1 and D5. It is a protein that in humans is encoded by the DRD1 gene. Tissue distribution D1 receptors are the most abundant kind of dopamine receptor in the central nervous system. Northern blot and in situ hybridization show that the gene expression, mRNA expression of DRD1 is highest in the dorsal striatum (caudate nucleus, caudate and putamen) and ventral striatum (nucleus accumbens and olfactory tubercle). Lower levels occur in the basolateral amygdala, cerebral cortex, septum, thalamus, and hypothalamus. The DRD1 gene expresses primarily in the caudate putamen in humans, and in the caudate putamen, the nucleus accumbens and the olfactory tubercle in mouse. Structure The dopamine receptor D1 (D1R) is a Gs-coupled GPCR characterized by a canonical seven-transmembrane (TM) helical domain, with a ligand-binding pocket located Extracellular space, extracellularl ...
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Dopamine Receptor D3
Dopamine receptor D3 is a protein that in humans is encoded by the ''DRD3'' gene. This gene encodes the D3 subtype of the dopamine receptor. The D3 subtype inhibits adenylyl cyclase through inhibitory G-proteins. This receptor is expressed in phylogenetically older regions of the brain, suggesting that this receptor plays a role in cognitive and emotional functions. It is a target for drugs which treat schizophrenia, drug addiction, and Parkinson's disease. Alternative splicing of this gene results in multiple transcript variants that would encode different isoforms, although some variants may be subject to nonsense-mediated decay (NMD). On a side note, it is also the Dopamine Receptor sub-type possessing the highest binding affinity for Dopamine itself and may explain why non- ergoline Dopamine Agonists are D3-preferring Function Alpha-synuclein (α-Syn) aggregation via Lewy bodies inclusion, a pathogenic signature exclusively present in PD patients, is decreased by D3 ago ...
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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, and obesity; it is also used to treat binge eating disorder in the form of its inactive prodrug lisdexamfetamine. Amphetamine was discovered as a chemical in 1887 by Lazăr Edeleanu, and then as a drug in the late 1920s. It exists as two enantiomers: levoamphetamine and dextroamphetamine. ''Amphetamine'' properly refers to a specific chemical, the Racemic mixture, racemic free base, which is equal parts of the two enantiomers in their pure amine forms. The term is frequently used informally to refer to any combination of the enantiomers, or to either of them alone. Historically, it has been used to treat nasal congestion and depression. Amphetamine is also used as an Performance-enhancing substance, athletic performance enhancer and Nootropic ...
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Dopamine Receptor D5
Dopamine receptor D5, also known as D1BR, is a protein that in humans is encoded by the ''DRD5'' gene. It belongs to the D1-like receptor family along with the D1 receptor subtype. Function D5 receptor is a subtype of the dopamine receptor that has a 10-fold higher affinity for dopamine than the D1 subtype. The D5 subtype is a G-protein coupled receptor, which promotes synthesis of cAMP by adenylyl cyclase via activation of Gαs/olf family of G proteins. Both D5 and D1 subtypes activate adenylyl cyclase. D1 receptors were shown to stimulate monophasic dose-dependent accumulation of cAMP in response to dopamine, and the D5 receptors were able to stimulate biphasic accumulation of cAMP under the same conditions, suggesting that D5 receptors may use a different system of secondary messengers than D1 receptors. Activation of D5 receptors is shown to promote expression of brain-derived neurotrophic factor and increase phosphorylation of protein kinase B in rat and mice prefr ...
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Dopamine Receptor D4
The dopamine receptor D4 is a dopamine D2-like G protein-coupled receptor encoded by the gene on chromosome 11 at 11p15.5. The structure of DRD4 has been reported in complex with the antipsychotic drug nemonapride. As with other dopamine receptor subtypes, the D4 receptor is activated by the neurotransmitter dopamine. It is linked to many neurological and psychiatric conditions including schizophrenia and bipolar disorder, ADHD, addictive behaviors, Parkinson's disease, and eating disorders such as anorexia nervosa. A weak association has been drawn between DRD4 and borderline personality disorder. It is also a target for drugs which treat schizophrenia and Parkinson's disease. The D4 receptor is considered to be D2-like in which the activated receptor inhibits the enzyme adenylate cyclase, thereby reducing the intracellular concentration of the second messenger cyclic AMP. Genetics The human protein is coded by the ''DRD4'' on chromosome 11 located in 11p15.5. Th ...
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Dopamine Receptor D2
Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the ''DRD2'' gene. After work from Paul Greengard's lab had suggested that dopamine receptors were the site of action of antipsychotic drugs, several groups, including those of Solomon H. Snyder and Philip Seeman used a radiolabeled antipsychotic drug to identify what is now known as the dopamine D2 receptor. The dopamine D2 receptor is the main receptor for most antipsychotic drugs. The structure of DRD2 in complex with the atypical antipsychotic risperidone has been determined. Function D2 receptors are coupled to Gi subtype of G protein. This G protein-coupled receptor inhibits adenylyl cyclase activity. In mice, regulation of D2R surface expression by the neuronal calcium sensor-1 (NCS-1) in the dentate gyrus is involved in exploration, synaptic plasticity and memory formation. Studies have shown potential roles for D2R in retrieval of fear memories in the prelimbic cortex and in d ...
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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 almost exclusively in the Andes. Indigenous peoples of South America, Indigenous South Americans have traditionally used coca leaves for over a thousand years. Notably, there is no evidence that habitual coca leaf use causes addiction or withdrawal, unlike cocaine. Medically, cocaine is rarely employed, mainly as a topical medication under controlled settings, due to its high abuse potential, adverse effects, and expensive cost. Despite this, recreational drug use, recreational use is widespread, driven by its euphoric and aphrodisiac properties. Levamisole induced necrosis syndrome (LINES)-a complication of the common cocaine Lacing (drugs), cutting agent levamisole-and prenatal cocaine exposure is particularly harmful. Street cocaine is ...
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Neuromodulatory
Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second messenger signaling cascade that induces a broad, long-lasting signal. This modulation can last for hundreds of milliseconds to several minutes. Some of the effects of neuromodulators include altering intrinsic firing activity, increasing or decreasing voltage-dependent currents, altering synaptic efficacy, increasing bursting activity and reconfiguring synaptic connectivity. Major neuromodulators in the central nervous system include: dopamine, serotonin, acetylcholine, histamine, norepinephrine, nitric oxide, and several neuropeptides. Cannabinoids can also be powerful CNS neuromodulators. Neuromodulators can be packaged into vesicles and released by neurons, secreted as hormones and delivered through the circulatory system. A neurom ...
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Neuroleptic
Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of other psychotic disorders. They are also the mainstay, together with mood stabilizers, in the treatment of bipolar disorder. Moreover, they are also used as adjuncts in the treatment of treatment-resistant major depressive disorder. The use of antipsychotics may result in many unwanted side effects such as involuntary movement disorders, gynecomastia, impotence, weight gain and metabolic syndrome. Long-term use can produce adverse effects such as tardive dyskinesia, tardive dystonia, tardive akathisia, and brain tissue volume reduction. The long term use of antipsychotics often changes the brain both structurally and chemically in a way that can be difficult or impossible to reverse. This can lead to lo ...
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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. Catechol can be either a free molecule or a substituent of a larger molecule, where it represents a 1,2-dihydroxybenzene group. Catecholamines are derived from the amino acid tyrosine, which is derived from dietary sources as well as synthesis from phenylalanine. Catecholamines are water-soluble and are 50% bound to plasma proteins in circulation. Included among catecholamines are epinephrine (adrenaline), norepinephrine (noradrenaline), and dopamine. Release of the hormones epinephrine and norepinephrine from the adrenal medulla of the adrenal glands is part of the fight-or-flight response. Tyrosine is created from phenylalanine by hydroxylation by the enzyme phenylalanine hydroxylase. Tyrosine is also ingested directly from dietary prote ...
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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 the origin of the dopaminergic cell bodies of the mesocorticolimbic dopamine system and other dopamine pathways; it is widely implicated in the drug and natural reward circuitry of the brain. The VTA plays an important role in a number of processes, including reward cognition ( motivational salience, associative learning, and positively-valenced emotions) and orgasm, among others, as well as several psychiatric disorders. Neurons in the VTA project to numerous areas of the brain, ranging from the prefrontal cortex to the caudal brainstem and several regions in between. Structure Neurobiologists have often had great difficulty distinguishing the VTA in humans and other primate brains from the substantia nigra (SN) and surrounding nuc ...
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Substantia Nigra
The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. ''Substantia nigra'' is Latin for "black substance", reflecting the fact that parts of the substantia nigra appear darker than neighboring areas due to high levels of neuromelanin in dopaminergic neurons. Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. Although the substantia nigra appears as a continuous band in brain sections, anatomical studies have found that it actually consists of two parts with very different connections and functions: the pars compacta (SNpc) and the pars reticulata (SNpr). The pars compacta serves mainly as a projection to the basal ganglia circuit, supplying the striatum with dopamine. The pars reticulata conveys signals from the basal ganglia to numerous other brain structures. Structure The substantia nigra, along with four other nuclei, is ...
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