Department of Psychology, The University of Texas at El Paso, El Paso, Texas.
Alcohol Clin Exp Res. 2014 Jan;38(1):108-15. doi: 10.1111/acer.12213. Epub 2013 Aug 1.
Ethanol (EtOH) abuse is a major health and economic concern, particularly for females who appear to be more sensitive to the rewarding effects of EtOH. This study compared sex differences to the rewarding and aversive effects of EtOH using place-conditioning procedures in rats.
Separate groups of adult (male, female, ovariectomized [OVX] female) and adolescent (male and female) rats received EtOH (0, 0.5, 1.0, 2.0, or 2.5 g/kg, intraperitoneal) and were confined to their initially nonpreferred side of our conditioning apparatus for 30 minutes. On alternate days, they received saline and were confined to the other side. Following 5 drug pairings, the rats were retested for preference behavior. Separate cohorts of the same groups of rats were injected with a similar dose range of EtOH, and blood EtOH levels (BELs) were compared 30 minutes later.
EtOH produced rewarding or aversive effects in a dose-dependent manner. An intermediate dose of EtOH (1.0 g/kg) produced rewarding effects in adult female, but not in male or OVX female rats, suggesting that ovarian hormones facilitate the rewarding effects of EtOH. Similarly, this intermediate dose of EtOH produced rewarding effects in adolescent female, but not in male rats. The highest dose of EtOH (2.5 g/kg) produced aversive effects that were similar across all adult groups. However, the aversive effects of EtOH were lower in adolescents than adults, suggesting that adolescents are less sensitive to the aversive effects of EtOH. The aversive effects of EtOH did not vary across the estrous cycle in intact adult females. There were also no group differences in BELs, suggesting that our results are not related to EtOH metabolism.
Our results in rats suggest that human females may be more vulnerable to EtOH abuse due to enhanced rewarding effects of this drug that are mediated by the presence of ovarian hormones.
乙醇（EtOH）滥用是一个主要的健康和经济问题，特别是对女性来说，她们似乎对 EtOH 的奖赏效应更为敏感。本研究使用大鼠位置条件反射程序比较了性别差异与 EtOH 的奖赏和厌恶效应。
成年（雄性、雌性、去卵巢雌性）和青春期（雄性和雌性）大鼠的不同组接受 EtOH（0、0.5、1.0、2.0 或 2.5 g/kg，腹腔内），并被限制在我们的条件反射仪器的最初非偏好侧 30 分钟。在交替的日子里，他们接受生理盐水并被限制在另一侧。在进行了 5 次药物配对后，大鼠再次进行偏好行为测试。同一组的不同队列大鼠接受类似剂量范围的 EtOH 注射，并在 30 分钟后比较血液 EtOH 水平（BEL）。
EtOH 以剂量依赖性方式产生奖赏或厌恶效应。中等剂量的 EtOH（1.0 g/kg）对成年雌性大鼠产生奖赏效应，但对雄性或去卵巢雌性大鼠没有产生奖赏效应，这表明卵巢激素促进了 EtOH 的奖赏效应。同样，这种中等剂量的 EtOH 对青春期雌性大鼠产生奖赏效应，但对雄性大鼠没有产生奖赏效应。最高剂量的 EtOH（2.5 g/kg）产生了相似的厌恶效应，所有成年组均如此。然而，青少年对 EtOH 的厌恶效应较低，这表明青少年对 EtOH 的厌恶效应不敏感。完整成年雌性大鼠的发情周期内 EtOH 的厌恶效应没有差异。BEL 也没有组间差异，这表明我们的结果与 EtOH 代谢无关。
我们在大鼠中的结果表明，由于卵巢激素介导的这种药物的奖赏效应增强，人类女性可能更容易受到 EtOH 滥用的影响。
