An anatomical and electrophysiological investigation of the serotonergic projection from the dorsal raphe nucleus to the substantia nigra in the rat

Evidence for a projection from the dorsal raphe nucleus to the substantia nigra was obtained by the demonstration of reactive perikarya in the dorsal raphe nucleus after injections of horseradish peroxidase into the substantia nigra of the rat. No labelled cells were observed in the median raphe nucleus. Stereotaxic injections of ³H]leucine into the dorsal raphe nucleus resulted in the appearance of autoradiographic grains over both the zona compacta and zona reticulate of the substantia nigra, although the concentration of grains was higher over the zona compacta. Electrolytic lesions of the dorsal raphe nucleus reduced nigral and striatal 5-hydroxytryptamine content by 61.5 and 70% respectively. Stimulation of the dorsal raphe nucleus was found to inhibit the unit activity of cells in both the zona compacta and zona reticulate of the substantia nigra and this inhibition could be blocked by 60–72 h pretreatment with p-chlorophenylalanine. Stimulation of the median raphe nucleus produced no consistent effects upon nigral unit activity. para-Chlorophenylalanine pretreatment did not significantly affect the rate of striatal dopamine depletion produced by injections of α-methyl-para-tyrosine, suggesting that the serotonergic raphe-nigral projection exerts a phasic rather than a tonic inhibitory influence over the dopaminergic neurons of the nigro-striatal projection.The results are discussed with reference to the possibility that the projections of the dorsal raphe nucleus to the substantia nigra and the striatum may mediate some of the interactions between central serotonergic and dopaminergic mechanisms.