Effects of cholecystokinin and related peptides on neuronal activity in the ventromedial nucleus of the rat hypothalamus

Abstract

1 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 μm) 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 micro-molar affinity for central CCK receptors. 3 Intracellular recordings from ventromedial nucleus neurones 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.