Effect of Neuropeptide Y (NPY) on Oral Ethanol Intake in Wistar, Alcohol-Preferring (P), and -Nonpreferring (NP) Rats

Background: Neuropeptide Y (NPY) deficient mice consume more ethanol than controls, whereas NPY over‐expressing mice consume less ethanol than controls. Thus, ethanol drinking may be inversely associated with NPY activity. To determine whether exogenously administered NPY would alter ethanol intake, two experiments were conducted. Methods: A within‐subject design was used with intracerebroventricular (ICV) administration of NPY or artificial cerebral spinal fluid (aCSF) into the lateral ventricles. Infusions were separated by 2 to 7 days. In experiment 1, male Wistar rats (n= 10) were tested for the effects of NPY on an intake of 5% sucrose or 8% (w/v) ethanol during daily 2‐hr testing periods with food and water available at all other times. In experiment 2, male alcohol‐preferring (P) and alcohol‐nonpreferring (NP) rats (n= 8/line) were tested for the effects of NPY on 8% (w/v) ethanol intake. Results: In experiment 1, NPY (5, 10, 20 μg) significantly increased sucrose intake relative to aCSF baseline in Wistar rats, a finding consistent with previous observations of the orexigenic effects of the peptide. However, NPY (10 μg) did not alter ethanol intake in Wistar rats. In experiment 2, NPY (5 and 10 μg) significantly decreased ethanol intake in P rats, but not in NP rats. Conclusion: The reduction in ethanol intake seen with the P rats is consistent with the postulated negative relationship between NPY activity and ethanol intake. The lack of effect of NPY on ethanol intake in Wistar and NP rats may be related to the lower baseline levels of ethanol intake in these rats or to differential central nervous system basal NPY activity or sensitivity to the peptide.