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 c ontrols, whereas NPY over-expressing mice consume less ethanol than control s. Thus, ethanol drinking may be inversely associated with NPY activity. To determine whether exogenously administered NP 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 inta ke 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 teste d for the effects of NPY on 8% (w/v) ethanol intake. Results: In experiment 1, NPY (5, 10, 20 mug) significantly increased sucro se intake relative to aCSF baseline in Wistar rats, a finding consistent wi th previous observations of the orexigenic effects of the peptide. However, NPY (10 mug) did not alter ethanol intake in Wistar rats. In experiment 2, NPY (5 and 10 mug) significantly decreased ethanol intake in P rats, but n ot in NP rats. Conclusion: The reduction in ethanol intake seen with the P rats is consist ent with the postulated negative relationship between NPY activity and etha nol intake. The lack of effect of NPY on ethanol intake in Wistar and NP ra ts may be related to the Lower baseline levels of ethanol intake in these r ats or to differential central nervous system basal NPY activity or sensiti vity to the peptide.