Serotonergic Innervation of the Forebrain: Effect of Lesions on Serotonin and Tryptophan Hydroxylase Levels

Concentrations of serotonin and tryptophan hydroxylase activity in individual hypothalamic and limbic nuclei, as well as cortical regions, were measured by radioenzymatic microassays after dorsal raphe nucleus lesions and various surgical transections of the brain stem. Fourteen days after lesioning of the dorsal raphe nucleus there were 43-65% decreases in 5-HT concentrations of certain hypothalamic and limbic nuclei. More pronounced decreases were found in the parietal cortex and in the locus coeruleus and substantia nigra. Degenerations of nerve terminals in various regions of the hypothalamus and the limbic system were detected by electron microscopic studies 1-8 days after dorsal raphe nucleus lesions. There was no change in the 5-HT concentration of the spinal cord following dorsal raphe nucleus lesions. Surgical transections at the level of mesencephalic-pontine junction caused no significant changes in 5-HT concentrations or tryptophan hydroxylase levels in the hypothalamus, limbic system, cerebral cortex or spinal cord. Serotonergic fibers ascending from the mesencephalic raphe nuclei constitute a well circumscribed bundle dorsal to the interpeduncular nucleus. The axons enter the hypothalamus between the mammillary body and crus cerebri just ventral to the medial forebrain bundle. The ascending pathway contains all the ascending 5-HT fibers innervating the hypothalamus and the rostral limbic and cortical areas.