Cholecystokinin reduces ethanol consumption in golden hamsters

Abstract 

In experimental conditions, golden hamsters (Mesocricetus auratus) avidly consume ethanol solutions. However, they are relatively resistant to the deleterious effects of ethanol even after months of continuous consumption, apparently because they metabolize ethanol rapidly and efficiently. Male hamsters with ad libitum access to food and water were presented with isocaloric solutions [weight/weight (wt./wt.)] of 10% ethanol and 17.75% glucose for 40-min periods on alternate days. When hamsters were injected with 0.9% saline before solution presentation the mean intake of ethanol solution (0.55 g) was about half that of glucose solution (1.08 g). Hamsters derived a mean of 0.36 g/kg/40 min of absolute ethanol from the ethanol solution, an amount that does not seem to exceed their metabolic capacity for ethanol. An intraperitoneal injection of a 2.0-μg/kg dose of the C-terminal octapeptide of cholecystokinin (CCK-8) reduced intakes of both solutions by >50% if administered 5 min before solution presentation, but it was ineffectual if administered 45 min before presentation. When citric acid (2.5 g/l) was added to the glucose solution the baseline intakes of the two solutions were virtually equivalent, and when CCK-8 was administered over a range of doses (0.5–2.0 μg/kg) the intakes of the solutions did not differ significantly at any dose, supporting the suggestion that the pharmacological properties of ethanol play little or no role in mediating the consumption-inhibiting effect of exogenously administered cholecystokinin (CCK). Prior administration of lorglumide, a selective CCK type A receptor antagonist, completely attenuated the inhibitory effect of CCK-8. Findings are consistent with the notion that endogenous CCK plays a key role in the short-term control of ethanol intake in hamsters.

Keywords: Golden hamster, Alcohol, Ethanol intake, Limited-access procedure, Cholecystokinin, CCK-8, Lorglumide