Sex differences in adult Wistar rats in the voluntary consumption of ethanol after pre-exposure to ethanol-induced flavor avoidance learning

Torre, M. Lourdes de la; Escarabajal, Ma Dolores; Zapata, Ángeles Agüero

doi:10.1016/j.pbb.2015.07.011

Cited by 23 publications

(13 citation statements)

References 59 publications

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“…We found that females reached a higher EtOH consumption level and exhibited greater high-drinking days than males. These findings are consistent with previous studies showing that female rodents drink more EtOH than males [22][23][24][25] and exhibit less aversion to EtOH, as demonstrated by conditioned taste aversion using EtOH-saccharin pairings [27][28][29], with males developing an aversion after only one pairing and females after the third pairing and only at higher doses of EtOH [28]. Other groups have reported that the rewarding effects of EtOH are enhanced in females and therefore, may be hormone-dependent [56], which may explain the increased EtOH intake over time that may lead to increases in potential for overconsumption.…”

Section: Plos Onesupporting

confidence: 93%

“…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].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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Background Forced alcohol (ethanol, EtOH) exposure has been shown to cause significant impairments on reversal learning, a widely-used assay of cognitive flexibility, specifically on fully-predictive, deterministic versions of this task. However, previous studies have not adequately considered voluntary EtOH consumption and sex effects on probabilistic reversal learning. The present study aimed to fill this gap in the literature. Methods Male and female Long-Evans rats underwent either 10 weeks of voluntary intermittent 20% EtOH access or water only (H2O) access. Rats were then pretrained to initiate trials and learn stimulus-reward associations via touchscreen response, and subsequently required to select between two visual stimuli, rewarded with probability 0.70 or 0.30. In the final phase, reinforcement contingencies were reversed. Results We found significant sex differences on several EtOH-drinking variables, with females reaching a higher maximum EtOH consumption, exhibiting more high-drinking days, and escalating their EtOH at a quicker rate compared to males. During early abstinence, EtOH drinkers (and particularly EtOH-drinking females) made more initiation omissions and were slower to initiate trials than H2O drinking controls, especially during pretraining. A similar pattern in trial initiations was also observed in discrimination, but not in reversal learning. EtOH drinking rats were unaffected in their reward collection and stimulus response times, indicating intact motivation and motor responding. Although there were sex differences in

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Section: Plos Onesupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…Sex differences in alcohol intake and preference are well recognized in animals and humans, with females generally drink more alcohol than males [30][31][32][53][54][55]. Consistent with this, average daily alcohol intake in female Bmal1CTR mice was significantly greater than in Bmal1CTR males (P<0.0001, unpaired two-tailed t test) and mean alcohol preference was significantly higher in Bmal1CTR females than Bmal1CTR males (P<0.05, unpaired two-tailed t test) ( Supplementary Fig.…”

Section: Deletion Of Bmal1 or Per2 From Msns Eliminates Sex Differencsupporting

confidence: 66%

Sexually dimorphic influence of the circadian clock geneBmal1in the striatum on alcohol intake

Zavalía¹,

Schöttner²,

Goldsmith³

et al. 2020

Preprint

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SummaryThe clock gene Bmal1 plays an obligatory role in the generation of circadian rhythms in gene expression, physiology, and behavior in mammals [1–4]. In mice, perturbations in Bmal1 expression in the brain are associated with loss of circadian rhythmicity and various physiological and behavioral disturbances, including disrupted sleep architecture and deficits in cognitive and affective behaviors [5–14]. Gene association studies in both humans and animals suggest that Bmal1 may also play a role in the control of appetitive behaviors such as alcohol preference and consumption [15–19]. Although there is evidence that genes that interact with Bmal1 in the molecular circadian clock, such as Per2 and Clock influence alcohol intake and preference [15, 20–23], experimental evidence of a causal role of Bmal1 is lacking. In addition, the specific brain regions where Bmal1 might affect alcohol consumption are not known. We investigated voluntary alcohol consumption in conditional knockout mice that lack BMAL1 protein exclusively in the striatum, which is an important structure in the control of alcohol intake and preference [24–29]. Particular emphasis was attributed to the investigation of male and female mice because of known sex differences in alcohol intake and preference [30–32], and the impact of a sexually dimorphic constitution of circadian clocks on behavior [33, 34]. We found that deletion of BMAL1 from the principal medium spiny neurons (MSNs) of the striatum significantly altered voluntary alcohol intake and preference, without affecting total fluid intake, sucrose preference, body weight, or circadian rhythms in behavior. Strikingly, there were major sex differences in the effect of striatal BMAL1 deletion on alcohol consumption. While striatal BMAL1 deletion augmented alcohol intake and preference in males, the same deletion suppressed intake and preference in females. Interestingly, striatal deletion of PER2, a clock gene that interacts with Bmal1 in the circadian clock, and which has been shown to limit alcohol consumption in mice [22], mimicked the effect of striatal BMAL1 deletion, albeit only in males. Together, our results reveal that BMAL1 in MSNs of the striatum plays a sexually dimorphic role in the control of alcohol intake in mice, restraining consumption in males, possibly by interacting with PER2, and promoting intake in females, independently of PER2. We therefore hypothesize that a sex-specific mechanism in the function of BMAL1 in MSNs of the striatum regulates differences between male and female mice in the propensity to consume alcohol.

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“…None the less, future studies are needed to further investigating the appetitive and motivational impact of adult alcohol exposure. Previous studies have shown that pre-exposure to ethanol in adulthood increased future consumption (de la Torre, Escarabajal & Agüero, 2015; Carrara-Nascimento, Olive & Camarini, 2014). While pre-exposure increased consumption in both adolescent and young adult rats, it modestly increased the motivation to consume alcohol in the adolescent-exposed rats compared to controls.…”

Section: Discussionmentioning

confidence: 99%

Alcohol drinking during adolescence increases consumptive responses to alcohol in adulthood in Wistar rats

Amodeo

Kneiber

Wills

et al. 2017

Alcohol

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Binge drinking and the onset of alcohol use disorders usually peak during the transition between late adolescence and early adulthood, and early adolescent onset of alcohol consumption has been demonstrated to increase the risk for alcohol dependence in adulthood. In the present study we describe an animal model of early adolescent alcohol consumption where animals drink unsweetened and unflavored ethanol in high concentrations (20%). Using this model we investigated the influence of drinking on alcohol-related appetitive behavior and alcohol consumption levels in early adulthood. Further, we also sought to investigate whether differences in alcohol-related drinking behaviors were specific to exposure in adolescence versus exposure in adulthood. Male Wistar rats were given a 2-bottle choice between 20% ethanol and water in one group and between two water bottles in another group during their adolescence (Postnatal Day (PD) PD26-59) to model voluntary drinking in adolescent humans. As young adults (PD85), rats were trained in a paradigm that provided free access to 20% alcohol for 25 min after completing up to a fixed ratio (FR) 16-lever press response. A set of young adult male Wistar rats was exposed to the same paradigm using the same time course beginning at PD92. The results indicate that adolescent exposure to alcohol increased consumption of alcohol in adulthood. Furthermore, when investigating differences between adolescent high and low adolescent drinkers in adulthood, high consumers continued to drink more alcohol, had fewer FR failures, and had faster completion of FR schedules in adulthood whereas the low consumers were no different than controls. Rats exposed to ethanol in young adulthood also increased future intake but there were no differences in any other components of drinking behavior. Both adolescent- and adult-exposed rats did not exhibit an increase in lever pressing during the appetitive challenge session. These data indicate that adolescent and early adult alcohol exposure can increase consumptive aspects of drinking but that adolescent exposure may preferentially influence the motivation to drink.

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Sex differences in adult Wistar rats in the voluntary consumption of ethanol after pre-exposure to ethanol-induced flavor avoidance learning

Cited by 23 publications

References 59 publications

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

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

Sexually dimorphic influence of the circadian clock geneBmal1in the striatum on alcohol intake

Alcohol drinking during adolescence increases consumptive responses to alcohol in adulthood in Wistar rats

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