Ethanol abstinence -related behaviors and the effects of neuropeptide Y on these behaviors in animals genetically and environmentally susceptible to ethanol dependence

Abstract

Central neuropeptide Y (NPY) and ethanol share similar behavioral profiles in animals. NPY suppresses ethanol drinking in alcohol-preferring (P) rats and this effect is augmented following a period of ethanol abstinence. Increased NPY activity also suppresses operant responding for ethanol in outbred animals that are physically dependent on ethanol. The purpose of experiment 1 was to examine the effects of NPY on anxiety as measured by light-enhanced acoustic startle (L-E ASR) testing in P rats that had undergone cycles of ethanol drinking and ethanol abstinence (ABST group) and in ethanol-naïve P rats (NAÏVE group). ABST rats were given six weeks of access to 15% (v/v) ethanol and water followed by two weeks with no ethanol, two weeks with ethanol, and three more weeks with no ethanol. All rats were infused intracerebroventricularly (ICV) with one of four NPY doses on day 14 of abstinence period two, and tested for anxiety (pre- and post-footshock) and feeding. Rats were again infused with NPY on day 20 of abstinence period 2 and tested for feeding. NPY dose-dependently increased food intake regardless of ethanol drinking history and footshock exposure. NPY suppressed anxiety-like behavior similarly in all rats. The purpose of experiment 2 was to examine the effects of NPY on ethanol drinking and feeding in Wistar rats that had undergone chronic ethanol vapor exposure, cycles of ethanol abstinence, both, or no ethanol exposure. Ethanol-drinking Wistars were given six weeks of access to 15% (v/v) ethanol and water followed by either: two cycles of one week ethanol vapor exposure and two weeks with no ethanol; two cycles of one week ethanol bottle availability and two weeks with no ethanol; or two weeks of ethanol vapor exposure. All rats were infused ICV with one of four NPY doses following ethanol exposure patterns described above, and tested for ethanol drinking and feeding in a 2-bottle choice situation. NPY dose-dependently increased food intake regardless of ethanol exposure history, but suppressed ethanol drinking only in rats that underwent cycles of ethanol access and ethanol abstinence. These results support the notion that dysregulation of brain NPY systems may be important in the motivational factors for relapse to ethanol drinking