Behavioral indicators of succeeding and failing under higher-challenge compulsion-like alcohol drinking in rat

Darevsky, David; Hopf, F. Woodward

doi:10.1016/j.bbr.2020.112768

Cited by 30 publications

(67 citation statements)

References 48 publications

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“…This finding is in line with other measures of motivation (e.g. licking bout, time-course of consumption) where others have demonstrated that compulsive-like QuA drinking is accompanied by consummatory behaviors associated with motivation for alcohol drinking (Darevsky et al, 2019;Darevsky and Hopf, 2020). Additionally, when we compared frontloading of QuA to nonadulterated alcohol at baseline in the alcohol history mice we found that QuA significantly reduced front-loading relative to baseline.…”

Section: Discussionsupporting

confidence: 90%

Three Weeks of Binge Alcohol Drinking Generates Increased Alcohol Front‐Loading and Robust Compulsive‐Like Alcohol Drinking in Male and Female C57BL/6J Mice

Bauer

McVey

Boehm

2021

Alcoholism Clin & Exp Res

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Background Current models of compulsive‐like quinine‐adulterated alcohol (QuA) drinking in mice, if improved, could be more useful for uncovering the neural mechanisms of compulsive‐like alcohol drinking. The purpose of these experiments was to further characterize and improve the validity of a model of compulsive‐like QuA drinking in C57BL/6J mice. We sought to determine whether compulsive‐like alcohol drinking could be achieved following 2 or 3 weeks of Drinking‐in‐the‐Dark (DID), whether it provides evidence for a robust model of compulsive‐like alcohol drinking by inclusion of a water control group and use of a highly concentrated QuA solution, whether repeated QuA exposures alter compulsive‐like drinking, and whether there are sex differences in compulsive‐like alcohol drinking. Methods Male and Female C57BL/6J mice were allowed free access to either 20% alcohol or tap water for 2 hours each day for approximately 3 weeks. After 2 or 3 weeks, the mice were given QuA (500 μM) and the effect of repeated QuA drinking sessions on compulsive‐like alcohol drinking was assessed. 3‐minute front‐loading, 2 hour binge‐drinking, and blood alcohol concentrations were determined. Results Compulsive‐like QuA drinking was achieved after 3 weeks, but not 2 weeks, of daily alcohol access as determined by alcohol history mice consuming significantly more QuA than water history mice and drinking statistically nondifferent amounts of QuA than nonadulterated alcohol at baseline. Thirty‐minute front‐loading of QuA revealed that alcohol history mice front‐loaded significantly more QuA than water history mice, but still found the QuA solution aversive. Repeated QuA exposures did not alter these patterns, compulsive‐like drinking did not differ by sex, and BACs for QuA drinking were at the level of a binge. Conclusions These data suggest that compulsive‐like QuA drinking can be robustly achieved following 3 weeks of DID and male and female C57BL/6J mice do not differ in compulsive‐like alcohol drinking.

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Section: Discussionsupporting

confidence: 90%

Three Weeks of Binge Alcohol Drinking Generates Increased Alcohol Front‐Loading and Robust Compulsive‐Like Alcohol Drinking in Male and Female C57BL/6J Mice

Bauer

McVey

Boehm

2021

Alcoholism Clin & Exp Res

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“…We modeled drug consumption despite negative consequences by adulterating oxycodone solution with increasing doses of quinine, which is commonly used to assess compulsive alcohol drinking [106,107]. While the quinine concentrations were quite low relative to ethanol studies, oxycodone is an alkaloid with a bitter taste prior to the introduction of quinine and already aversive, which we confirmed by establishing that naïve mice avoid 1.0 mg/mL oxycodone before the introduction of quinine (Fig S1A).…”

Section: Discussionmentioning

confidence: 62%

Modeling features of addiction with an oral oxycodone self-administration paradigm

Murphy

Chang

Pareta

et al. 2021

Preprint

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Prescription opioid use is an initiating factor driving the current opioid epidemic. There are several challenges with modeling prescription opioid addiction. First, prescription opioids such as oxycodone are orally self-administered and have different pharmacokinetics and dynamics than morphine or fentanyl. This oral route of administration determines the pharmacokinetic profile, which is critical for establishing reliable drug-reinforcement associations in animals. Second, intravenous opioid self-administration is typically performed with intermittent drug self-administration sessions in a separate environment from the home cage. This does not recapitulate prescription opioid use, which is characterized by continuous drug access in the patients homes. To model features of prescription opioid use and the transition to abuse, we developed an oxycodone self-administration paradigm that is administered in the homecage. Mice voluntarily self-administer oxycodone in this paradigm without any taste modification such as sweeteners, and exhibit preference for oxycodone, escalation of intake, physical signs of dependence, reinstatement of seeking after withdrawal, and a subset of animals demonstrate drug taking that is resistant to negative consequences. This model is therefore translationally relevant and can be useful for studying the neurobiological substrates specifically relevant to prescription opioid abuse.

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“…Briefly, as detailed in Methods, data are combined from two large female/male cohorts, and, within each rat, we examined intake and licking patterns in two sessions from each of the four different drinking conditions: AOnly, alcohol with moderate challenge (i.e., AQ10), and alcohol with higher challenge (AQ60 or AQ100), tested in randomized order. Also, as described in Methods, and as we [47, 55] and others [66, 67] have done, we analyzed responding across sessions or bouts separate from the animal identities.…”

Section: Resultsmentioning

confidence: 99%

“…Lickometry analyses were performed as we previously published [47, 55]. We examined licking which was aggregated into bouts, where a bout is defined as 3 licks with <1sec between licks, which we previously used based on extensive previous literature (discussed in [55]).…”

Section: Methodsmentioning

confidence: 99%

“…However, under higher challenge, females retained several behaviors which were impaired in males, including greater intake relative to the number of licks, and the ability to generate longer bouts earlier in the session. Faster licking has been linked to greater motivation and vigor (see [47, 55]), but the noted differences in female responding were not accompanied by changes in average licking speed, and female intake level under alcohol-only and moderate challenge were unlinked from licking speed, unlike males where slower licking predicted lower intake. Finally, we find no impact of estrous cycle on female drinking.…”

Section: Introductionmentioning

confidence: 99%

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

Sergio

Darevsky

Soares

et al. 2022

Preprint

Self Cite

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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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Behavioral indicators of succeeding and failing under higher-challenge compulsion-like alcohol drinking in rat

Cited by 30 publications

References 48 publications

Three Weeks of Binge Alcohol Drinking Generates Increased Alcohol Front‐Loading and Robust Compulsive‐Like Alcohol Drinking in Male and Female C57BL/6J Mice

Three Weeks of Binge Alcohol Drinking Generates Increased Alcohol Front‐Loading and Robust Compulsive‐Like Alcohol Drinking in Male and Female C57BL/6J Mice

Modeling features of addiction with an oral oxycodone self-administration paradigm

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

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