Cholecystokinin and bombesin inhibit ethanol and food intake in rats selectively bred for ethanol sensitivity.

Cholecystokinin octapeptide (CCK-8) and bombesin tetradecapeptide (BBS-14) are brain-gut neuropeptides shown to inhibit intake and choice of alcohol solutions and foods in a variety of species. Recently, Draski and colleagues selectively bred strains descended from N/Nih outbred Norway rats that differ in sleep time after injection of ethanol. The intake of 5% w/v ethanol, food, and water was measured in these rats with high, low, and control alcohol sensitivity (HAS, LAS, and CAS), after intraperitoneal injection of randomized sequences of doses of CCK-8 or BBS-14 (0-8 micrograms/kg). During baseline adaptation to water deprivation-induced consumption of alcohol, LAS rats consumed reliably more ethanol than HAS or CAS rats. Injection of CCK-8 or BBS-14 significantly and equivalently suppressed intake of ethanol and food at 30 min after presentation in each group of rats. Water intake and food intake at 30-60 min following alcohol access was not affected by prior injection of either neuropeptide. Large differences in alcohol neurosensitivity (HAS > CAS > LAS) were observed in these rats' resting behavior for 1 hr after intraperitoneal injection of 1 g/kg of ethanol. These selectively bred alcohol neurosensitivity differences cannot be explained by corresponding differences in sensitivity to the inhibitory behavioral effects of CCK-8 or BBS-14. However, differences in alcohol intake and resting behavior do correspond to artificially selected sensitivities to ethanol's hypnotic effect.