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 individually and concomitantly into the slice chamber. CCK-8S (0.1-2.5 microM) produced a dose-dependent increase in firing rate mainly mediated by the CCK(B) receptor subtype, because Suc-CCK-4 (a CCK(B) receptor agonist) acted like CCK-8S and A-71378 (a CCK(A) receptor agonist) rarely induced excitatory effects. The main response to serotonin application (2-20 microM) was an inhibition that could be mimicked by 8-OH-DPAT (a 5-HT1A receptor agonist). S-UH-301 (a 5-HT1A receptor antagonist) reversibly diminished or blocked this effect. Other 5-HT agonists like DOI and 2-Methyl-5-HT did not evoke relevant responses. Co-administration of CCK-8S and 5-HT induced counteracting effects at which CCK-8S significantly reduced the prevailing suppressive effect of serotonin. It is concluded that both substances, CCK and 5-HT, have a reciprocal influence on the regulation of neuronal activity within the VMH, a structure, which is involved in the mediation of signals for the state of satiety.