Neuropeptide Y reduces oral ethanol intake in alcohol-preferring (P) rats following a period of imposed ethanol abstinence

Background: Intracerebroventricular infusion of NPY has been shown to reduce ethanol intake in alcohol-preferring (P) rats in a limited access procedure. The purpose of the present investigation was to extend this finding to a two-bottle free-choice continuous access procedure in groups of rats that either did or did not undergo a period of imposed ethanol abstinence and ethanol reinstatement. Methods: In experiment 1, female P rats were given 6 weeks of continuous access to ethanol (8% w/v) and water. Ethanol was removed for a period of 2 weeks during which the rats were surgically implanted with a cannula into the lateral ventricle. Following the ethanol abstinence period and immediately before ethanol reinstatement, rats received a single infusion of either artificial cerebrospinal fluid or NPY (10 mug). Ethanol and water intake was measured at both 4 hr and 24 hr after infusion, and 24-hr intake measures were taken daily for 13 postinfusion days. Experiment 2 was run in parallel with experiment 1, with the exception that rats did not undergo a period of imposed ethanol abstinence. Also, food intake was measured 4 and 24 hr after infusion. Results: Following 2 weeks of imposed ethanol abstinence (experiment 1), NPY suppressed ethanol intake through postinfusion day 2. After uninterrupted continuous access to ethanol (experiment 2), NPY suppressed ethanol intake to a lesser extent and this effect lasted only 24 hr. NPY increased food intake at the 4-hr but not the 24-hr measure. Conclusions: Previous findings that central administration of NPY suppresses ethanol intake in P rats are extended by this study to a continuous access procedure, and the effect is amplified following a period of imposed ethanol abstinence. This effect of NPY compares favorably to results obtained with other treatments tested in similar animal models and provides support for a role of NPY in an allostasis model of addiction.