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

Abstract Sardinian alcohol-preferring (sP) rats have been selectively bred, over almost forty years, for high alcohol preference and consumption. sP rats have served as animal model 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. Accordingly, alcohol self-administration under the fixed ratio 4 schedule of reinforcement was compared among male, intact female, and ovariectomized female sP rats. Additionally, it was investigated whether (i) estrous cycle influenced alcohol self-administration and (ii) alcohol self-administration in the 3 sP rat groups differed in sensitivity to pharmacological manipulation. Lever-responding for alcohol was 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 (in g/kg) did not differ among the 3 sP rat groups or occasionally was 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 and (ii) positively correlated with number of lever-responses for alcohol and estimated amount of self-administered alcohol. Treatment with the opioid receptor antagonist, naloxone (0, 0.3, 1, and 3 mg/kg, i.p.), and the positive allosteric modulator of the GABA B 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, these results provide the first characterization of alcohol-seeking and -taking behavior in female sP rats.