Ter-O’Hagen et al., 2009) or there were no significant sex differences
Ter-O’Hagen et al., 2009) or there were no considerable sex variations in alcohol intake (Albrechet-Souza et al., 2020; Fulenwider et al., 2019; Lorrai et al., 2019; Priddy et al., 2017; Randall et al., 2017; Tavares et al., 2019). The source of these inconsistences isn’t clear. By utilizing the 4 core genotype (FCG) mouse model, it’s feasible to uncouple the effects of sex chromosomes and developmental TLR8 Agonist MedChemExpress gonadal hormones (Finn, 2020; Puralewski et al., 2016) and their influence more than ethanol drinking. In FCG mice, the testes-determining gene is excised from the Y chromosome and reincorporated into the genome as an autosomal transgene. The Y sex chromosome is hence decoupled from the improvement of gonads and production of gonadal hormones. Using the FCG model, gonadal females consume more alcohol than gonadal males in an operant self-administration paradigm, independent of the sex chromosome complement (Barker et al., 2010; Finn, 2020). This suggests that the higher alcohol consumption in females might be attributed for the organizational effects of developmental gonadal hormones on neural circuits. Additionally, neonatal exposure to testosterone facilitates male-like differentiation via its organizational effects. In female rodents, neonatal testosterone is promptly aromatized to estrogen, and this exposure to testosterone-derived estrogen reduces alcohol intake to mimic the reduced alcohol consumption in intact males (Almeida et al., 1998; Finn, 2020). These studies suggest that the organizational effects of neonatal testosterone is critical for minimizing alcohol intake in non-dependent males. The activational effects of sex homones on ethanol drinking are also evident (Table 1). In gonadectomized adult male rodents, dihydrotestosterone reduces alcohol intake in two-bottle option paradigms whereas estradiol increases alcohol intake (Almeida et al., 1998; HilakiviClarke, 1996). Research investigating how the estrous cycle impacts alcohol intake, also because the activational effects of estradiol and progesterone in females, have yielded mixed findings. Frequently, alcohol intake doesn’t fluctuate more than the estrous cycle in two-bottle choice and operant self-administration paradigms in rodents (Ford et al., 2002; Fulenwider et al., 2019; Lorrai et al., 2019; Priddy et al., 2017; Scott et al., 2020). In non-human NLRP3 Agonist manufacturer primates nevertheless, alcohol self-administration is significantly larger during the luteal phase on the menstrual cycle in comparison with the follicular phase (Dozier et al., 2019). The peak alcohol intake follows the progesterone peak during the luteal phase when progesterone levels are rapidly decreasing, suggesting that progesterone may possibly impact alcohol intake in female monkeys (Dozier et al., 2019). In contrast, progesterone therapy does not have an effect on alcohol self-administration in ovariectomized female rats (Almeida et al., 1998). Similarly, serum estradiol levels usually do not correlate with ethanol intake throughout self-administration in female monkeys (Dozier et al., 2019); but estradiol reduces two-bottle decision alcohol intake in female rodents (Almeida et al., 1998; Hilakivi-Clarke, 1996). This is unlikely to be related to the rewarding properties of ethanol since estradiol facilitates ethanol-conditioned location preference (Almeida et al., 1998; Finn, 2020; Hilderbrand Lasek, 2018). Notably, whileAlcohol. Author manuscript; available in PMC 2022 February 01.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptPrice and McCoolPageethan.