University of Houston, Department of Psychology & Texas Institute for Measurement, Evaluation and Statistics (TIMES), Houston, TX 77204-6022, United States.
University of Houston, Department of Psychology & Texas Institute for Measurement, Evaluation and Statistics (TIMES), Houston, TX 77204-6022, United States.
Pharmacol Biochem Behav. 2018 Apr;167:50-59. doi: 10.1016/j.pbb.2018.02.003. Epub 2018 Feb 24.
The mu-opioid antagonist, naltrexone (NTX), is a FDA-approved treatment for alcohol use disorder (AUD); however, the data on whether it differentially affects males vs. females are mixed. NTX increases hypothalamic-pituitary-adrenal (HPA) axis activity that associates with subjective responses to alcohol and craving in individuals with AUD. The present study tested for sex differences in the ability of NTX to decrease appetitive and consummatory behaviors in rats in operant alcohol self-administration. Because the opioid system and HPA axis are sexually dimorphic, we examined NTX's effect on adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels.
Male and female Sprague-Dawley rats (n's = 6-8) were trained to lever press for alcohol (10% v/v) under a fixed-ratio 2 schedule of reinforcement. NTX doses (0, 0.1-10 mg/kg) were assessed in tests conducted under a progressive ratio schedule of reinforcement. Separate groups of alcohol and water drinking rats (n's = 8) were used to assess NTX's (10 mg/kg) effects on HPA axis hormones.
NTX decreased consummatory behaviors for alcohol in a dose-related manner, but not appetitive behaviors in males. In females, NTX decreased appetitive behaviors for alcohol in a dose-dependent manner, but only decreased consummatory behaviors at the highest (10 mg/kg) NTX dose. NTX increased ACTH levels in alcohol drinking females in diestrus, but not in other groups. However, NTX increased CORT levels for longer durations in alcohol drinking males relative to alcohol drinking females in diestrus.
Our findings suggest that NTX selectively reduces consummatory behaviors for alcohol in males and appetitive behaviors in females, while also showing differential sex effects on HPA hormones.
μ-阿片受体拮抗剂纳曲酮（NTX）是美国食品和药物管理局批准的治疗酒精使用障碍（AUD）的药物；然而，关于它是否能区分男性和女性的效果的数据存在差异。NTX 增加了下丘脑-垂体-肾上腺（HPA）轴的活性，与 AUD 患者对酒精的主观反应和渴望有关。本研究测试了 NTX 降低雄性和雌性大鼠在操作性酒精自我给药中摄食和消费行为的能力是否存在性别差异。由于阿片系统和 HPA 轴存在性别二态性，我们检查了 NTX 对促肾上腺皮质激素（ACTH）和皮质酮（CORT）水平的影响。
雄性和雌性 Sprague-Dawley 大鼠（n=6-8）接受训练，通过固定比率 2 强化程序按压杠杆以获得酒精（10%v/v）。在递增比率强化程序测试中评估了 NTX（0、0.1-10mg/kg）的剂量。使用分别的酒精和水饮用大鼠组（n=8）来评估 NTX（10mg/kg）对 HPA 轴激素的影响。
NTX 以剂量相关的方式减少了雄性的酒精消费行为，但不影响其摄食行为。在雌性中，NTX 以剂量依赖的方式减少了酒精的摄食行为，但仅在最高（10mg/kg）NTX 剂量下才减少了消费行为。NTX 增加了发情期雌性酒精饮用大鼠的 ACTH 水平，但在其他组中没有增加。然而，与发情期雌性酒精饮用大鼠相比，NTX 使雄性酒精饮用大鼠的 CORT 水平升高的时间更长。
我们的发现表明，NTX 选择性地减少了雄性的酒精消费行为和雌性的摄食行为，同时对 HPA 激素也表现出性别差异效应。
