INTERACTIVE EFFECTS OF CHOLECYSTOKININ-8S AND SEROTONIN ON SPONTANEOUSLY ACTIVE NEURONS IN VENTROMEDIAL HYPOTHALAMIC SLICES

The influence of cholecystokinin (CCK-8S) and serotonin (5-HT) on the discharge rate of spontaneously active ventromedial hypothalamic (VMH) neurons was investigated in brain slices. Drugs were drop-applied ind ividually and concomitantly into the slice chamber. CCK-8S (0.1-2.5 mu M) produced a dose-dependent increase in firing rate mainly mediated by the CCKB receptor subtype, because Suc-CCK-4 (a CCKB receptor agoni st) acted like CCK-8S and A-71378 (a CCKA receptor agonist) rarely ind uced excitatory effects. The main response to serotonin application (2 -20 mu M) was an inhibition that could be mimicked by 8-OH-DPAT (a 5-H T1A receptor agonist). S-UH-301 (a 5-HT1A receptor antagonist) reversi bly diminished or blocked this effect. Other 5-HT agonists like DOI an d 2-Methyl-5-HT did not evoke relevant responses. Co-administration of CCK-8S and 5-HT induced counteracting effects at which CCK-8S signifi cantly reduced the prevailing suppressive effect of serotonin. It is c oncluded that both substances, CCK and 5-HT, have a reciprocal influen ce on the regulation of neuronal activity within the VMH, a structure, which is involved in the mediation of signals for the state of safety .