An investigation into the effects of cholecystokinin octapeptide (CCK-8S) and its pentapeptide analogue, pentagastrin, on neurones located in ventromedial nuclei of rat hypothalamic slices maintained in vitro has been undertaken. 2. CCK-8S (0.01-1.0 microM) applied in the perfusion medium produced a concentration-dependent increase in firing rate. This effect could be mimicked by pentagastrin and was selectively blocked by L-364,718, a potent peripheral CCK receptor antagonist that has been shown to possess micromolar affinity for central CCK receptors. 3. Intracellular recordings from ventromedial nucleus neurons revealed two distinct populations with comparable resting membrane parameters but differing neuronal activity. One group fired tetrodotoxin (TTX)-sensitive action potentials spontaneously at resting membrane potential whilst the second group fired action potentials only on injection of depolarizing current and were otherwise silent. 4. Application of CCK-8S or pentagastrin to spontaneously active neurones produced a small depolarization concomitant with an increase in action potential firing rate but the peptides had no effect on membrane properties of 'silent' neurones. 5. These data suggest the existence of at least two populations of neurones in the ventromedial hypothalamus, only one of which is excited by CCK-8S and pentagastrin.
