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 investigated 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. Perfusion of tetrodotoxin (TTX, 1 mu M and 10 mu M) into the dorsal raphe simultaneously decreased dorsal raphe and hippocampal 5-HT release. However, following TTX perfusion into the hippocampus (10 mu M), hippocampal 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 concentrations in the dorsal raphe and in the hippocampus. The decreases in raphe and hippocampal 5-HT induced by systemic buspirone were antagonized in rats pretreated with 1.0 mM (-) pindolol, locally perfused into the dorsal raphe. Local dorsal raphe perfusion of (-) pindolol alone (0.01-1.0 mM) increased dorsal raphe 5-HT and concomitantly induced a small 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 provide evidence that 5-HT release in the dorsal raphe is dependent on the opening of fast activated sodium channels and that dorsal raphe 5-HT1A receptors control somatodendritic and hippocampal 5-HT release.