Unequal interactions between alcohol and nicotine co-consumption: Suppression and enhancement of concurrent drug intake

DeBaker, Margot C.; Moen, Janna K.; Robinson, Jenna M.; Wickman, Kevin; Lee, AM

doi:10.1101/601641

Cited by 8 publications

(5 citation statements)

References 53 publications

(22 reference statements)

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“…Our results agree with previous findings showing no sex differences in basic aversion sensitivity for quinine [78–80] or shock [81]. We also find that aversion-resistance across doses of quinine was not different between females and males, agreeing with previous studies showing sex-similar quinine sensitivity in alcohol under home cage bottle-drinking conditions ([80,82,83] but see [75]). However, other studies have found that females can be more aversion-resistant, including under operant responding for alcohol [79] and shock-resistance in a place preference model [81].…”

Section: Discussionsupporting

confidence: 93%

Evidence for different greater-persistence strategies under lower and higher challenge for alcohol in female rats

Sergio

Darevsky

Soares

et al. 2022

Preprint

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Problem alcohol drinking is a substantial social and economic burden. Studies show that the misuse of alcohol is increasing in women, and that women can face higher consequences from alcohol exposure, but females have historically been understudied. Thus, there is considerable interest in understanding potential sex-different and -similar cognitive/emotional strategies, and underlying mechanisms, for alcohol responding, which would inform more effective, personalized treatments. Here, we used large cohorts of adult Wistar rats (28 females, 30 males) to provide robust assessment of potential sex differences in responding for alcohol-only and under compulsion-like drinking with moderate or higher challenge (since intake despite negative consequences can be a major obstacle to human treatment). Females had similar total licking but higher intake for all drinking conditions. However, females had significantly longer bouts under alcohol-only and moderate challenge, but not higher challenge. Further, under higher challenge, females retained several aspects of responding not seen in males, including more efficient lick volume and earlier onset of longer bouts. In addition, females overall licked slightly faster, but licking speed averaged within-bout showed no sex differences, and female intake level under alcohol-only and moderate challenge was unlinked from licking speed (unlike males, where slower licking predicted lower intake). We interpret these differences as greater persistence-like responding but not vigor per se in females, and with different strategies under lower versus higher challenge. Finally, drinking levels did not differ across the estrous cycle, although ovariectomy reduced alcohol-only and moderate-challenge intake. Together, while many aspects were sex-similar, suggesting some common drinking mechanisms, there was clear evidence for (perhaps more nuanced) sex-different alcohol strategies, which might make an outsized contribution to excessive drinking since women can have more drinking problems. Thus, our studies provide important context for future work examining sex differences in pathological drinking mechanisms.

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Section: Discussionsupporting

confidence: 93%

Evidence for different greater-persistence strategies under lower and higher challenge for alcohol in female rats

Sergio

Darevsky

Soares

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…We also found that CIE vapor inhalation selectively impacted aversion-resistant drinking in male, but not female rats. We found no impact of sex independently of CIE vapor inhalation, consistent with some prior reports (DeBaker et al, 2020;Randall et al, 2017;Sneddon et al, 2018), but not others (Fulenwider et al, 2019;Sneddon et al, 2020). Prior reports examining the impact of CIE vapor inhalation on aversion-resistant drinking have not, to our knowledge, included female subjects (Vendruscolo et al, 2012), though differences in other measures of compulsive alcohol seeking have been reported (Xie et al, 2019).…”

Section: Sex Differences In Ethanol Consumption and The Effects Of Ci...supporting

confidence: 90%

Alcohol availability during withdrawal gates the impact of alcohol vapor exposure on responses to alcohol cues

et al. 2022

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Background: Chronic intermittent ethanol (CIE) vapor inhalation is a widely used model of alcohol dependence, but the impact of CIE on cue-elicited alcohol seeking is not well understood. Here, we assessed the effects of CIE on alcohol-seeking elicited by previously learned cues, and on acquisition of new cue-alcohol associations. Methods:In Experiment 1, male and female Long Evans rats were first trained in a discriminative stimulus (DS) task, in which one auditory cue (the DS) predicts the availability of 15% ethanol and a control cue (the NS) predicts nothing. Rats then underwent CIE or served as controls. Subsets of each group received access to oral ethanol twice a week during acute withdrawal. After CIE, rats were presented with the DS and NS cues under extinction and retraining conditions to determine whether they would alter their responses to these cues. In Experiment 2, rats underwent CIE prior to training in the DS task. We also assessed alcohol consumption, aversion-resistant drinking, somatic withdrawal symptoms, and behavior in an open field. Results:We found that CIE enhanced behavioral responses to previously learned alcohol cues, but only in rats that received access to alcohol during acute withdrawal. CIE disrupted cue responses in rats that did not. When CIE occurred before cue learning, male rats were slower to develop cue responses and less likely to enter the alcohol port, even though they had received alcohol during acute withdrawal. We also found that CIE increased alcohol consumption and aversion-resistant drinking in male but not female rats.Conclusions: These results suggest that CIE alone does not potentiate the motivational value of alcohol cues, but that an increase in cue responses requires the potentiation of the value of alcohol during acute withdrawal. Further, under some conditions CIE may disrupt responses to previously learned and subsequently acquired alcohol cues.

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“…Greater aversion resistance in female versus male mice has also been demonstrated for oral fentanyl consumption in the home cage, but not the operant chamber (Monroe & Radke, 2020). It is important to note that not all studies have found sex differences in aversion resistance (Bauer, McVey, & Boehm, 2021; DeBaker, Moen, Robinson, Wickman, & Lee, 2020; Sneddon et al., 2019), further demonstrating the importance of the behavioral paradigm in revealing female vulnerability to addictive behavior. See Table 1 for more information.…”

Section: Female Vulnerability In Drug Self‐administration Studiesmentioning

confidence: 99%

Studying Sex Differences in Rodent Models of Addictive Behavior

2021

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Animal models of addictive behaviors are useful for uncovering neural mechanisms involved in the development of dependence and for identifying risk factors for drug abuse. One such risk factor is biological sex, which strongly moderates drug self‐administration behavior in rodents. Female rodents are more likely to acquire drug self‐administration behaviors, consume higher amounts of drug, and reinstate drug‐seeking behavior more readily. Despite this female vulnerability, preclinical addiction research has largely been done in male animals. The study of sex differences in rodent models of addictive behavior is increasing, however, as more investigators are choosing to include both male and female animals in experiments. This commentary is meant to serve as an introductory guide for preclinical investigators new to the study of sex differences in addiction. We provide an overview of self‐administration models, a broad view of female versus male self‐administration behaviors, and suggestions for study design and implementation. Inclusion of female subjects in preclinical addiction research is timely, as problem drug and alcohol use in women is increasing. With proper attention, design, and analysis, the study of sex differences in addiction has the potential to uncover novel neural mechanisms and lead to greater translational success for addiction research. © 2021 Wiley Periodicals LLC

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Unequal interactions between alcohol and nicotine co-consumption: Suppression and enhancement of concurrent drug intake

Cited by 8 publications

References 53 publications

Evidence for different greater-persistence strategies under lower and higher challenge for alcohol in female rats

Evidence for different greater-persistence strategies under lower and higher challenge for alcohol in female rats

Alcohol availability during withdrawal gates the impact of alcohol vapor exposure on responses to alcohol cues

Studying Sex Differences in Rodent Models of Addictive Behavior

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