title: 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.
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects*; D011903:Raphe Nuclei / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism
chemical_list: D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D003000:Clonidine; D001058:Apomorphine