Sex differences and hormonal modulation of ethanol-enhanced risk taking in rats

Abstract

Background Ethanol (EtOH) intake correlates with increased risk-taking, and sex differences exist in both EtOH use and risk-taking in humans and rats. However, the interaction of sex and gonadal hormones to affect risk-taking under the influence of EtOH has not been determined. This was the focus of the current study. Methods Adult Long-Evans rats (n=18 males and females) were gonadectomized and received hormone replacement at physiologic levels or blank implants (n=7–9/group). Risk-taking was assessed with probability discounting, requiring rats to choose between a small/certain reward and a large/uncertain reward delivered with decreasing probability throughout each daily session. Before testing, rats received saline or EtOH (0.5 or 1.0 g/kg) ip. Results In males, EtOH increased preference for the large/uncertain reward lever (F2,28=10.462, p<0.05). However, there was no effect of EtOH on lever preference in females (F1,30=0.914, p>0.05). At baseline, ORCHX+T males showed a greater preference for the large/uncertain reward lever then ORCHX males (F1,14=13.805, p<0.05). In females only, EtOH decreased choice latency relative to baseline (F1,10=7.25, p<0.05). EtOH decreased loss sensitivity in both sexes, with all rats exhibiting decreased lose-shift ratios (males: F2,18=5.10, p<0.05; females F2,10=4.37, p<0.05). Conclusions These results show that EtOH, sex, and hormones interact to influence decision making. EtOH increases risk taking in males, but not in females. However, EtOH selectively decreases choice latency in females, and decreases loss sensitivity in both sexes. These findings are relevant to understanding human behavior, particularly in adolescents who experience increased hormone levels and often drink EtOH and engage in risky behavior.

Risk-based Decision Making in Rats: Modulation by Sex and Amphetamine

“…Gonadectomy has been shown to influence some aspects in decision-making in males (Tan and Vyas, 2016;Wallin-Miller et al, 2017) and females (Uban et al, 2012). However, in the present study, gonadectomy did not exert changes in risky choices in either males or females.…”

“…This discrepancy can be due the different types of costs that were associated with larger rewards across different tasks (Tan and Vyas, 2016;Uban et al, 2012), or the rewards used (Wallin-Miller et al, 2017), as in the later study risky choices were elicited by ethanol, and this stimulus could have a stronger impact on motivation and on the mesolimbic reward pathway. The idea that sex-hormone regulation of decision making can differ depending on the type of cost associated with larger/preferred rewards is further bolstered by the findings of studies examining how stress affects these processes.…”

Androgen Regulation of the Mesocorticolimbic System and Executive Function

“…Therefore, circulating androgens may enhance ethanol effects on behavior, potentially increasing risk-taking in one or both sexes. To address this possibility, a study compared GDX male and female rats with and without hormone replacement in the probability discounting task, to investigate the influence of ethanol and gonadal steroids on the response to uncertainty ( 202 ). At baseline, GDX + T males showed a greater preference for the large reward than GDX males.…”

Sex-dependent effects of chronic intermittent voluntary alcohol consumption on attentional, not motivational, measures during probabilistic learning and reversal

“…We probed these in the present study. Also noteworthy, most studies have exclusively used male animals, limiting the generalizability of the results given recent findings showing sex differences in consumption patterns, with female rodents showing higher EtOH intake levels and preference for EtOH [22][23][24][25][26], even exhibiting less aversion to EtOH compared to males [27][28][29][30].…”