NEURONAL RELEASE OF SEROTONIN IN THE CEREBELLUM OF BEHAVING RATS - ANIN-VIVO MICRODIALYSIS STUDY

Release of endogenous serotonin [5-hydroxytryptamine (5-HT)] in the ce rebellum of awake rats was characterized using in vivo microdialysis. 5-HT output was increased (similar to 70%) by local application of KCI (100 mM) and was reduced (similar to 60%) by both tetrodotoxin (0.5 m u M) and omission of Ca2+ from the perfusion fluid. 5-HT release was d ecreased (similar to 70%) by the selective 5-HT1A agonist 8-hydroxy-2- (di-n-propylamino)tetralin (0.25 mg/kg, s.c.), and this effect was rap idly reversed by a selective 5-HT1A antagonist, N-[2-[4-(2-methoxyphen yl)-1-piperazinyl] ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihy drochloride (WAY-100635; 0.1 mg/kg, i.p.), These results indicate that a large portion of the measurable 5-HT output in the cerebellum is of neuronal origin, is dependent on impulse flow, and is sensitive to 5- HT1A autoreceptor activation. Further studies examined the relationshi p between 5-HT levels and general activity of the animals across the l ight-dark transition and during behavioral manipulations. Both 5-HT le vels and behavioral activity were significantly elevated during the da rk period, with changes in 5-HT efflux closely paralleling changes in activity. Similar increases (similar to 40%) in 5-HT output were obser ved during both feeding and feeding in the presence of a stressor (tai l pinch). These findings suggest that behavioral state is an important factor determining neuronal 5-HT release in cerebellum under physiolo gical conditions.