Effect of the Cerebral Tryptaminergic System on the Turnover of Dopamine in the Striatum of the Rat

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Abstract
The effect of the cerebral 5-hydroxytryptamine [5-HT] system on the turnover of striatal 3,4-dihydroxyphenylethylamine (dopamine) [DA] was investigated by measuring the level of DA and one of its metabolites in rats depleted of cerebral 5-HT or treated with a 5-HT receptor blocker. Treatment with p-chlorophenylalanine [p-CPA] induced, in addition to a reduction in striatal 5-HT and 5-hydroxyindol-3-ylacetic acid [5-HIAA], an increase in the striatal concentration of DA, a diminution in the concentration of homovanillic acid [HVA] in the same cerebral area and a reduction in the rise of this acid after the administration of a butyrophenone derivative or tetrabenazine. Treatment with methysergide also reduced the increase of HVA induced by the butyrophenone. When probenecid was given to rats treated with p-CPA, HVA failed to accumulate, whereas the accumulation of 5-HIAA was unaffected. The decay of DA after .alpha.-methyl-p-tyrosine administration was normal for the first 6 h but was later reduced in rats given p-CPA or methysergide. Evidently, the lack of activation of 5-HT receptors leads to a reduction in the turnover of DA in the nigrostriatal pathway.