Serotonin (5-HT) release in the dorsal raphé and ventral hippocampus: raphé control of somatodendritic and terminal 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 raphé and ventral hippocampus in freely moving rats. Perfusion of tetrodotoxin (TTX, 1 microM and 10 microM) into the dorsal raphé simultaneously decreased dorsal raphé and hippocampal 5-HT release. However, following TTX perfusion into the hippocampus (10 microM), hippocampal 5-HT release was profoundly reduced but dorsal raphé 5-HT remained unchanged. Systemic injections with 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 raphé and in the hippocampus. The decreases in the raphé and hippocampal 5-HT induced by systemic buspirone were antagonized in rats pretreated with 1.0 mM (-) pindolol, locally perfused into the dorsal raphé. Local dorsal raphé perfusion of (-) pindolol alone (0.01-1.0 mM) increased dorsal raphé 5-HT and concomitantly induced a small increase in hippocampal 5-HT. Buspirone perfusion into the dorsal raphé did not change (10 nM, 100 nM), or produced a small increase (1.0 mM) in raphé 5-HT, without changing hippocampal 5-HT. These data provide evidence that 5-HT release in the dorsal raphé is dependent on the opening of fast activated sodium channels and that dorsal raphé 5-HT1A receptors control somatodendritic and hippocampal 5-HT release