Female rats display enhanced rewarding effects of ethanol that are hormone dependent - PubMed (original) (raw)

Female rats display enhanced rewarding effects of ethanol that are hormone dependent

Oscar V Torres et al. Alcohol Clin Exp Res. 2014 Jan.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Adolescence; Alcohol; Aversion; Reward; Sex Differences.

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Figures

Figure 1

Place conditioning produced by various doses of ethanol (0, 0.5, 1.0, 2.0, or 2.5 g/kg, ip) in adult male (n=11-20), adult female (n=8-30), and OVX female (n=7-14), adolescent male (n=6-10), and adolescent female (n=7-9) rats. The data are presented as difference scores (±SEM), which reflect time spent in the initially non-preferred side after conditioning minus before conditioning such that values above “0” reflect a positive shift in preference (CPP) and values below “0” represent an a negative shift in preference (CPA). Asterisks (*) denote a significant difference from respective saline controls, daggers (†) reflect a difference from respective male counterparts at a particular dose, and number signs (#) reflect a difference from respective adult counterparts at a particular dose (p < 0.05).

Figure 2

Place conditioning produced by ethanol (2.5 g/kg) in adult females that were tested during estrus (n=8), diestrus (n=5). metestrus (n=5), or proestrus (n=6). The data are presented as difference scores (±SEM), which reflect time spent in the initially non-preferred side after conditioning minus before conditioning such that values below “0” represent a negative shift in preference (CPA).

Figure 3

Plasma BELs 30 minutes after administration of various doses of ethanol (0.5, 1.0 or 2.0, g/kg, ip) in adult male (n=5 per dose), adult female (n=4-5 per dose), OVX female (n=4-5 per dose), adolescent male (n=10 per dose), and adolescent female (n=5-6 dose) rats. The asterisks (*) denote a significant increase in BELs relative to the lowest dose of ethanol (0.5 g/kg) collapsed across treatment groups (p < 0.05).

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Female rats display enhanced rewarding effects of ethanol that are hormone dependent - PubMed (original) (raw)