EXTRACELLULAR 5-HYDROXYTRYPTAMINE IN MEDIAN RAPHE NUCLEUS OF THE CONSCIOUS RAT IS DECREASED BY NANOMOLAR CONCENTRATIONS OF 8-HYDROXY-2-(DI-N-PROPYLAMINO) TETRALIN AND IS SENSITIVE TO TETRODOTOXIN

Extracellular 5-hydroxytryptamine (5-HT) in the median raphe and dorsa l hippocampus was measured using in vivo microdialysis. Administration of 60 mM K+ through the probe into the median raphe region significan tly increased 5-HT output from the median raphe and the right dorsal h ippocampus. Local infusion of 10 mu M tetrodotoxin into the median rap he region substantially decreased 5-HT in the median raphe and left an d right dorsal hippocampus. Systemic administration (0.3 mg/kg s.c.) o f 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) decreased the 5-H T levels in the dialysates from both the median raphe region and dorsa l hippocampus. Administration of 30 nM 8-OH-DPAT through the dialysis probe into the median raphe region decreased 5-HT output from the medi an raphe and dorsal hippocampus significantly, whereas at concentratio ns from 60 nM to 10 mu M no significant effects were found in either r egion. With 100 mu M 8-OH-DPAT, a significant increase was seen in the median raphe region, but not in dorsal hippocampus. Similar findings were obtained following microinjections of different doses of the comp ound into the median raphe region. The results of this study indicate that the somatodendritic release of 5-HT is impulse flow-dependent. Mo reover, the decrease of 5-HT in the median raphe region by low nanomol ar concentrations of 8-OH-DPAT supports the notion that somatodendriti c 5-HT release is subject to a local negative feedback mechanism throu gh 5-HT(1)A autoreceptors.