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The nucleus accumbens–possible site of antipsychotic action of neuroleptic drugs?

Published online by Cambridge University Press:  09 July 2009

T. J. Crow ,
J. F. W. Deakin  and
A. Longden
T. J. Crow*
Affiliation:
Division of Psychiatry, Clinical Research Centre and Division of Physiology and Pharmacology, National Institute for Medical Research, London
J. F. W. Deakin
Affiliation:
Division of Psychiatry, Clinical Research Centre and Division of Physiology and Pharmacology, National Institute for Medical Research, London
A. Longden
Affiliation:
Division of Psychiatry, Clinical Research Centre and Division of Physiology and Pharmacology, National Institute for Medical Research, London
*
1Address for correspondence: Dr T. J. Crow, Division of Psychiatry, Clinical Research centre, Northwick Park Hospital, Watford Rd, Harrow, Middx HA1 3UJ
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Synopsis

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.

Type
Research Article
Information
Psychological Medicine , Volume 7 , Issue 2 , May 1977 , pp. 213 - 221
Copyright
Copyright © Cambridge University Press 1977

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