Effects of clonidine, piperoxane and locus coeruleus lesion on the serotonergic and dopaminergic systems in raphe and caudate nucleus

Abstract

To assess the influences of central noradrenergic neurons on both serotonergic and dopaminergic systems, the neurochemical effects of clonidine, piperoxane, and 6-hydroxydopamine were examined. Using quantitative fluorescence histochemistry and high performance liquid chromatography, we have demonstrated that clonidine, much like apomorphine, preferentially augmented intracellular serotonin (5-HT) fluorescence in the dorsal raphe without affecting 5-HT cells in the median raphe nucleus. Clonidine also produced a significant decrease of extraperikaryal catecholamine (CA) fluorescence in the same region. Piperoxane, at a dose having no significant effect alone, antagonized the effects of clonidine on 5-HT and CA. 6-Hydroxydopamine lesions of the locus coeruleus produced a similar increase of 5-HT fluorescence in the dorsal raphe and decrease of CA fluorescence in both the dorsal and median raphe. Biochemically, clonidine decreased while piperoxane increased a measure of 5-HT turnover in the corresponding terminal region of the dorsal raphe, the striatum. Similarly, dopamine turnover was also decreased by clonidine and increased by piperoxane in the striatum. These effects may be mediated by noradrenergic projections from the locus coeruleus to both the dorsal raphe and the substantia nigra. These results support the hypothesis that the effects of clonidine on serotonergic and dopaminergic neurons are indirectly mediated through noradrenergic receptor stimulation.