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Additive effects of apomorphine and clonidine on serotonin neurons in the dorsal raphe
Abstract:
Effects of apomorphine (APO) and clonidine (CLON) on the mesostriatal and mesolimbic serotonergic systems were examined in the present study. Both drugs selectively elevated serotonin (5-HT) concentrations in the dorsal raphe and the striatum without significantly altering 5-HT measures in the median raphe and the hippocampus. Apomorphine also increased tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) levels in the dorsal raphe and 5-HIAA level in the striatum. Clonidine did not markedly alter tryptophan and 5-HIAA measures, while it decreased 5-HT turnover rate in both region, as indicated by the ratio of 5-HIAA/5-HT levels. Co-administration of APO and CLON, at doses of each drug exerted maximum effects on 5-HT alone, produced an additive effect on 5-HT in the dorsal raphe, while their effects on 5-HT and 5-HIAA in the striatum were counteracting each other. Effects of APO on 5-HT and 5-HIAA were attributed to the elevation of 5-HT precursor tryptophan, while effects of CLON on 5-HT and 5-HIAA were due to a decreased rate of 5-HT turnover. Therefore, the present results support the hypothesis that the additive effects of APO and CLON on dorsal raphe 5-HT are mediated through different receptors and neuropharmacological mechanisms.
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