The nucleus accumbens--possible site of antipsychotic action of neuroleptic drugs? 1977

T J Crow, and J F Deakin, and A Longden

The hypothesis that neuroleptic drugs exert their therapeutic effects by blocking dopaminergic transmission has been investigated by examining the effects of 3 neuroleptic drugs on dopamine turnover in 2 dopaminergically innervated regions of brain--the neostriatum and nucleus accumbens. The drugs chlorpromazine, thioridazine and fluphenazine, known to be therapeutically active in the treatment of schizophrenia, but to have differing incidences of extrapyramidal side effects, were administered to rats in dose ratios approximating to those effective in man. All 3 drugs induced a similar rise in the content of the dopamine metabolite homovanillic acid (HVA) in the nucleus accumbens, whilst the changes in HVA observed in the neostriatum were in the rank order in which these drugs produce extrapyramidal side effects. While the concentrations of dopamine metabolites in the frontal cortex were too low to assess the possibility that neuroleptic drugs have actions at this level, our results are consistent with the hypothesis that these drugs exert their therapeutic effects by dopamine receptor blockade in the nucleus accumbens.

UI MeSH Term Description Entries
D008297 Male Males
D011618 Psychotic Disorders Disorders in which there is a loss of ego boundaries or a gross impairment in reality testing with delusions or prominent hallucinations. (From DSM-IV, 1994) Psychoses,Psychosis, Brief Reactive,Schizoaffective Disorder,Schizophreniform Disorders,Psychosis,Brief Reactive Psychoses,Brief Reactive Psychosis,Disorder, Psychotic,Disorder, Schizoaffective,Disorder, Schizophreniform,Disorders, Psychotic,Disorders, Schizoaffective,Disorders, Schizophreniform,Psychoses, Brief Reactive,Psychotic Disorder,Reactive Psychoses, Brief,Reactive Psychosis, Brief,Schizoaffective Disorders,Schizophreniform Disorder
D011954 Receptors, Dopamine Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells. Dopamine Receptors,Dopamine Receptor,Receptor, Dopamine
D002746 Chlorpromazine The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking DOPAMINE RECEPTORS. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. Aminazine,Chlorazine,Chlordelazine,Chlorpromazine Hydrochloride,Contomin,Fenactil,Largactil,Propaphenin,Thorazine,Hydrochloride, Chlorpromazine
D003342 Corpus Striatum Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE. Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005476 Fluphenazine A phenothiazine used in the treatment of PSYCHOSES. Its properties and uses are generally similar to those of CHLORPROMAZINE. Flufenazin,Fluphenazine Hydrochloride,Lyogen,Prolixin,Hydrochloride, Fluphenazine
D006719 Homovanillic Acid A 3-O-methyl ETHER of (3,4-dihydroxyphenyl)acetic acid. 3-Methoxy-4-Hydroxyphenylacetic Acid,4-Hydroxy-3-Methoxyphenylacetic Acid,3 Methoxy 4 Hydroxyphenylacetic Acid,4 Hydroxy 3 Methoxyphenylacetic Acid,Acid, 3-Methoxy-4-Hydroxyphenylacetic,Acid, 4-Hydroxy-3-Methoxyphenylacetic,Acid, Homovanillic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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