Operant, oral alcohol self-administration: Sex differences in Sardinian alcohol-preferring rats

Sardinian alcohol-preferring (sP) rats have been selectively bred, over almost forty years and for more than 100 generations, for high alcohol preference and consumption. Rats of the sP line have served as animal model of excessive alcohol consumption for more than 120 published studies. With very few exceptions however, these studies have always employed male sP rats, and little is known on alcohol-related behaviors in female sP rats. The present study was designed to fill, at least in part, this gap. To this end, operant self-administration of alcohol under the fixed ratio 4 schedule of reinforcement was compared between male, intact female, and ovariectomized female sP rats. Additional aims were (i) investigation of whether, and to which extent, estrous cycle influenced alcohol self-administration in sP rats and (ii) investigation of whether alcohol selfadministration in male, intact female, and ovariectomized female sP rats differed in sensitivity to pharmacological manipulation. Lever-responding for alcohol resulted to be steadily higher in male than intact and ovariectomized female sP rats; conversely, because of large sex differences in rat body weight, estimated amount of self-administered alcohol (expressed in g/kg) did not differ among the 3 sP rat groups or occasionally resulted to be higher in intact female than male and ovariectomized female sP rats. Blood alcohol levels deriving from self-administered alcohol (i) did not differ among the 3 sP rat groups, (ii) achieved values known to result in measurable psychopharmacological effects, and (iii) positively correlated with both number of lever-responses for alcohol and estimated amount of self-administered alcohol. Treatment with both the opioid receptor antagonist, naloxone (0, 0.3, 1, and 3 mg/kg, i.p.), and the positive allosteric modulator of the GABAB receptor, GS39783 (0, 25, 50, and 100 mg/kg, i.g.), reduced alcohol self-administration with comparable potency and efficacy in the 3 sP rat groups. Impact of estrous cycle on alcohol self-administration was relatively modest, limited to a tendency toward a reduction in number of lever-responses for alcohol and estimated amount of self-administered alcohol in estrus and metestrus. Together, the results of the present study provide the first characterization of alcoholseeking and -taking behavior in female sP rats.