Neuroscience Institute, Section of Cagliari, National Research Council of Italy, I-09042, Monserrato (CA), Italy; Department of Biomedical Sciences, University of Cagliari, I-09042, Monserrato (CA), Italy.
Department of Biomedical Sciences, University of Sassari, I-07100, Sassari (SS), Italy.
Alcohol. 2019 Sep;79:147-162. doi: 10.1016/j.alcohol.2019.04.003. Epub 2019 Apr 26.
Sardinian alcohol-preferring (sP) rats have been selectively bred, over almost 40 years, for high alcohol preference and consumption. sP rats have served as an 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 about 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 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-administered alcohol (in g/kg) did not differ among the three sP rat groups or occasionally was higher in intact female than male and ovariectomized female sP rats. Blood alcohol levels derived from self-administered alcohol i) did not differ among the three sP rat groups and ii) were positively correlated with the number of lever-responses for alcohol and the estimated amount of self-administered alcohol. Treatment with the opioid receptor antagonist, naloxone (0, 0.3, 1, and 3 mg/kg, i.p. [intraperitoneally]), and the positive allosteric modulator of the GABA receptor, 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. The impact of the estrous cycle on alcohol self-administration was relatively modest, limited to a tendency toward 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 the first characterization of alcohol-seeking and -taking behavior in female sP rats.
撒丁岛酒精偏好（sP）大鼠经过近 40 年的选择性繁殖，具有高酒精偏好和消耗的特点。sP 大鼠已被用作 120 多项已发表研究的动物模型。然而，除了极少数例外，这些研究一直使用雄性 sP 大鼠，而对雌性 sP 大鼠的酒精相关行为知之甚少。本研究旨在至少部分填补这一空白。因此，比较了雄性、完整雌性和卵巢切除雌性 sP 大鼠在固定比例 4 强化程序下的酒精自我给药。此外，还研究了以下两个问题：i）发情周期是否影响酒精自我给药，以及 ii）三种 sP 大鼠组的酒精自我给药对药物处理的敏感性是否不同。雄性 sP 大鼠的酒精自我给药比完整和卵巢切除雌性 sP 大鼠的酒精自我给药更稳定；相反，由于大鼠体重的性别差异较大，估计的自我给药量（g/kg）在三种 sP 大鼠组之间没有差异，或者偶尔完整雌性 sP 大鼠的自我给药量比雄性和卵巢切除雌性 sP 大鼠的自我给药量高。从自我给药中获得的血液酒精水平：i）在三种 sP 大鼠组之间没有差异，ii）与酒精的 lever 反应次数和估计的自我给药量呈正相关。阿片受体拮抗剂纳洛酮（0、0.3、1 和 3mg/kg，腹腔内注射）和 GABA 受体正变构调节剂 GS39783（0、25、50 和 100mg/kg，灌胃）治疗降低了三种 sP 大鼠组的酒精自我给药，其效力和疗效相当。发情周期对酒精自我给药的影响相对较小，仅限于发情和间情期 lever 反应次数和估计的自我给药量减少的趋势。总的来说，这些结果首次描述了雌性 sP 大鼠的酒精寻求和摄取行为。
