Indirect effects of apomorphine on serotoninergic neurons in rats.
We have studied the effects of apomorphine on central serotoninergic system by using fluorescence histochemistry and high performance liquid chromatography coupled with electrochemical detection. Apomorphine has been shown selectively to elevate intracellular serotonin fluorescence in dorsal raphe neurons and serotonin and/or 5-hydroxyindoleacetic acid concentrations in the major terminal area of the dorsal raphe, the striatum. Apomorphine has no effect on serotonin neurons in the median raphe or its corresponding projection site, the hippocampus. In the present study, intraventricular 6-hydroxydopamine, when administered together with desimipramine and pargyline, antagonized the apomorphine-induced elevations of serotonin fluorescence in the dorsal raphe and serotonin and 5-hydroxyindoleacetic acid levels in the striatum. This antagonism was found when 6-hydroxydopamine was given either 3 or 10 days before 3 mg/kg apomorphine. Apomorphine also elevated extraperikaryal serotonin fluorescence and catecholamine fluorescence in the dorsal raphe selectively and these effects were also blocked by 6-hydroxydopamine. Additionally, 6-hydroxydopamine accelerated striatal serotonin turnover when it was given 10 days prior to death. This phenomenon probably reflects some compensatory change of mesostriatal serotonin neurons in response to the prolonged depletion of brain dopamine. The above results suggest that the observed effects of apomorphine on the serotoninergic system are mediated indirectly through dopaminergic neurons and that postsynaptic dopamine receptors are probably not responsible for apomorphine's effects.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001921:Brain / Q000502:physiology*; D006892:Hydroxydopamines / Q000633:toxicity; D006897:Hydroxyindoleacetic Acid / Q000502:physiology; D008297:Male; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*
D006892:Hydroxydopamines; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D016627:Oxidopamine; D001058:Apomorphine