SEROTONIN (5-HT) RELEASE IN THE DORSAL RAPHE AND VENTRAL HIPPOCAMPUS - RAPHE CONTROL OF SOMATODENDRITIC AND 5-HT RELEASE

Somatodendritic and terminal release of serotonin (5-HT) was investiga ted by simultaneously measuring extracellular concentrations of 5-HT, 5-hydroxyindole-3-acetic acid (5-HIAA) and homovanillic acid (HVA) in the dorsal raphe and ventral hippocampus in freely moving rats. Perfus ion of tetrodotoxin (TTX, 1 mu M and 10 mu M) into the dorsal raphe si multaneously decreased dorsal raphe and hippocampal 5-HT release. Howe ver, following TTX perfusion into the hippocampus (10 mu M), hippocamp al 5-HT release was profoundly reduced but dorsal raphe 5-HT remained unchanged. Systemic injections with the 5-HT1A agonist, buspirone (1.0 -5.0 mg/kg, i.p.) decreased 5-HT and 5-HIAA and increased HVA concentr ations in the dorsal raphe and in the hippocampus. The decreases in ra phe and hippocampal 5-HT induced by systemic buspirone were antagonize d in rats pretreated with 1.0 mM (-) pindolol, locally perfused into t he dorsal raphe. Local dorsal raphe perfusion of (-) pindolol alone (0 .01-1.0 mM) increased dorsal raphe 5-HT and concomitantly induced a sm all increase in hippocampal 5-HT. Buspirone perfusion into the dorsal raphe did not change (10 nM, 100 nM), or produced a small increase (1. 0 mM) in raphe 5-HT, without changing hippocampal 5-HT. These data pro vide evidence that 5-HT release in the dorsal raphe is dependent on th e opening of fast activated sodium channels and that dorsal raphe 5-HT 1A receptors control somatodendritic and hippocampal 5-HT release.