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

Sardinian alcohol-preferring (sP) rats have been selectively bred, over almost 40 years, for high alcoholpreference and consumption. sP rats have served as an animal model for more than 120 publishedstudies. With very few exceptions, however, these studies have always employed male sP rats, and littleis known about alcohol-related behaviors in female sP rats. The present study was designed tofill, atleast in part, this gap. Accordingly, alcohol self-administration under thefixed ratio 4 schedule ofreinforcement was compared among male, intact female, and ovariectomized female sP rats. Addition-ally, it was investigated whether i) estrous cycle influenced alcohol self-administration, and ii) alcoholself-administration in the three 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-administeredalcohol (in g/kg) did not differ among the three sP rat groups or occasionally was higher in intact fe-male than male and ovariectomized female sP rats. Blood alcohol levels derived from self-administeredalcohol i) did not differ among the three sP rat groups and ii) were positively correlated with the numberof lever-responses for alcohol and the estimated amount of self-administered alcohol. Treatment withthe opioid receptor antagonist, naloxone (0, 0.3, 1, and 3 mg/kg, i.p. [intraperitoneally]), and the positiveallosteric modulator of the GABABreceptor, GS39783 (0, 25, 50, and 100 mg/kg, i.g. [intragastrically]),reduced alcohol self-administration with comparable potency and efficacy in the three sP rat groups. Theimpact of the estrous cycle on alcohol self-administration was relatively modest, limited to a tendencytoward a reduction in the number of lever-responses for alcohol and the estimated amount of self-administered alcohol in estrus and metestrus. Together, these results provide thefirst characterizationof alcohol-seeking and -taking behavior in female sP rats.