Approximately 3.5 weeks following the last alcohol exposure, mice were placed in a clean, standard rat cage (26 cm l × 48 cm w × 20 cm h) with 5 cm of fresh, unscented bedding containing 20 evenly-spaced marbles. Following 30 min, the number of marbles buried, with a threshold of at least 2/3 of the marble being covered by bedding, was assessed by the experimenter and recorded. Novelty suppressed feeding

Lee KM, Coehlo M, McGregor HA, Waltermire RS, Szumlinski KK. Binge alcohol drinking elicits persistent negative affect in mice. Behav Brain Res. 2015;291:385–98. The first example shows the curls compared to sausages, the second hand with paws, and the third comparison of a skinner with the prince. As happens sometimes, a moment settled and hovered and remained for much more than a moment. And sound stopped and movement stopped for much, much more than a moment."Pang TY, Du X, Catchlove WA, Renoir T, Lawrence AJ, Hannan AJ. Positive environmental modification of depressive phenotype and abnormal hypothalamic-pituitary-adrenal axis activity in female C57BL/6J mice during abstinence from chronic ethanol consumption. Front Pharmacol. 2013;4:93. In this study, we found that the behavioral effects of protracted abstinence following chronic binge drinking were more robust in females, who demonstrate a behavioral disinhibition phenotype including reduced avoidance behavior and increased compulsive-like behavior (Fig. 7). These results underscore the importance of sex and timepoints into abstinence tested when investigating the effects of chronic alcohol on behavior. Indeed, the results of previous work on the affective behavioral consequences of chronic alcohol abstinence in C57BL/6 J mouse models are variable as to time into abstinence tested and paradigms utilized, as well as highly male-dominated [ 16]. Many studies have shown that males show increased avoidance, anhedonia, and compulsive behaviors in early abstinence (> 1 week) following chronic alcohol across vapor inhalation [ 34, 35, 36, 37, 38, 39], continuous access [ 21, 40], intermittent drinking [ 13], and DID [ 18, 22, 41, 42]. Behavior during protracted abstinence (< 1 week) in males is somewhat variable, with increased avoidance following chronic vapor [ 17] and DID [ 15, 18], with no effects following continuous [ 20, 21] and on most measures during intermittent access [ 10], and fairly consistent increased anhedonia across alcohol vapor [ 17, 19] and continuous drinking [ 20, 21, 40], with some exceptions for DID [ 18, 23]. Notably, an increase in avoidance behavior during abstinence in males has been broadly observed in the literature [ 16], in contrast to our observation of a reduction in this behavior and one other study that showed mild behavioral disinhibition in males and females following 7 weeks of intermittent alcohol access during early abstinence (24 h since last alcohol consumption [ 10]. It is possible that the variability of avoidance-related alterations following chronic alcohol consumption in males is due to differences in testing timepoints. Of Mice And Men' is set in the Great Depression era. The story revolves around two migrant ranch workers, George and Lennie, searching for a job as they move across America. Holleran KM, Wilson HH, Fetterly TL, Bluett RJ, Centanni SW, Gilfarb RA, et al. Ketamine and MAG lipase inhibitor-dependent reversal of evolving depressive-like behavior during forced abstinence from alcohol drinking. Neuropsychopharmacology. 2016;41(8):2062–71. Balogh KN, Mayes LC, Potenza MN. Risk-taking and decision-making in youth: relationships to addiction vulnerability. J Behav Addict. 2013. https://doi.org/10.1556/JBA.2.2013.1.1.

After George euthanized Lennie. Quotes From 'Of Mice And Men' Dealing With Friendship And Loneliness I seen things out here. I wasn't drunk. I don't know if I was asleep. If some guy was with me, he could tell me I was asleep, an' then it would be all right. But I jus' don't know." Desroches D, Orevillo C, Verina D. Sex- and strain-related differences in first-pass alcohol metabolism in mice. Alcohol. 1995;12(3):221–6.

Theme: A theme is a central idea that the novelist or the writer wants to stress upon. The novel not only shows man’s nature but also his situation in the grand design of the universe, his loneliness as well as man’s desire for relationships. Sneddon EA, White RD, Radke AK. Sex differences in binge-like and aversion-resistant alcohol drinking in C57BL/6J Mice. Alcohol Clin Exp Res. 2019;43(2):243–9. Well, I got a right to have a light. You go on get outa my room. I ain't wanted in the bunk house, and you ain't wanted in my room." Sure they all want it. Everybody wants a little bit of land, not much. Jus' som'thin' that was his. Som'thin' he could live on and there couldn't nobody throw him off of it. I never had none."

Bangasser DA, Wiersielis KR. Sex differences in stress responses: a critical role for corticotropin-releasing factor. Hormones (Athens). 2018;17(1):5–13. Nobody never gets to heaven, and nobody gets no land. It's just in their head. They're all the time talkin' about it, but it's jus' in their head." Bloch S, Holleran KM, Kash TL, Vazey EM, Rinker JA, Lebonville CL, et al. Assessing negative affect in mice during abstinence from alcohol drinking: limitations and future challenges. Alcohol. 2022;100:41–56. Thiele TE, Navarro M. “Drinking in the dark” (DID) procedures: a model of binge-like ethanol drinking in non-dependent mice. Alcohol. 2014;48(3):235–41.

Antagonist: Although it seems that the Great Depression is the main antagonist in the novel, it seems that it is an abstract idea that spread in the United States during the 30s. However, Curley is the actual antagonist, who tortures George and Lennie when they work on the farm of his father. Our results indicating sex differences in behavioral disinhibition during protracted abstinence led us to question whether the amount of cumulative alcohol consumption plays a role in the findings we observed here; that is, whether males would display a similar phenotype with additional alcohol drinking that achieved the cumulative alcohol consumption levels of females, or whether there are fundamental sex differences in the neural plasticity underlying these behavioral effects. Some studies report increased avoidance in males following acute abstinence from long term (8+ weeks) voluntary alcohol drinking [ 41] while others show no effect in some or all measures [ 42, 52] but to our knowledge, none have investigated these behaviors in protracted abstinence. Future work is necessary to further our understanding of the mechanism underlying our finding that post-chronic alcohol behavioral disinhibition is more pronounced in females and to dissect the role of risk-taking and compulsivity in binge drinking behavior to refine our understanding of the results in our study. Thus, there are sex differences underlying the physiological and behavioral responses to alcohol, and women may be more vulnerable to maladaptive effects that potentially drive future risky behaviors. Perspective and significance Full size image Behavioral disinhibition following a history of binge alcohol drinking was especially robust in females