Abstract
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.
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