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Browsing by Subject "Compulsion"
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Item Behavioral indicators of succeeding and failing under higher-challenge compulsion-like alcohol drinking in rat(Elsevier, 2020-09-01) Darevsky, David; Hopf, Frederic W.; Psychiatry, School of MedicineIntake despite negative consequences (compulsivity) contributes strongly to the harm of alcohol use disorder, making the underlying psychological and circuit mechanisms of great importance. To gain insight into possible underlying action strategies, we compared rat licking microstructure across compulsion-like and non-compulsive conditions. We previously showed that drinking under a moderate-challenge, quinine-alcohol model (Alc-ModQ) shows less variable responding in many measures, suggesting a more automatic strategy to overcome challenge. Here, we reanalyzed our original data, newly focusing on the behavioral profile of higher-challenge intake (100 mg/L quinine in alcohol, Alc-HighQ). Alc-HighQ greatly dropped consumption, yet retained aspects of greater automaticity and drive seen with Alc-ModQ, including earlier bout initiation and measures suggesting more stereotyped tongue control. In contrast, Alc-HighQ disordered bout generation and timing. Importantly, only fast-starting bouts persisted under Alc-HighQ, and while there were many fewer longer Alc-HighQ bouts, they still contributed >50 % of consumption. Also, longer bouts under Alc-HighQ had an early, several-second period with greater chance of stopping, but afterwards showed similar persistence and recovery from slow licking as other drinking conditions. Together, our findings elucidate novel behavioral indicators of successful and unsuccessful epochs of Alc-HighQ, compulsion-like intake. We also relate findings to congruent human and animal work implicating anterior insula and medial prefrontal cortices as critical for compulsion-like alcohol responding, and where ventral frontal cortex has been more associated with overall action plan and tongue control (retained under Alc-HighQ), with medial cortex more related to proximal action timing (disrupted under Alc-HighQ except after faster bout initiation).Item A Single Alcohol Pre-exposure Alters Dorsolateral Striatal AMPA Receptor Dependent Binge and Compulsive-like Drinking(2020-12) Bauer, Meredith R.; Boehm, Stephen L.; Logrip, Marian; Grahame, NicholasBackground Compulsive alcohol drinking is a defining characteristic of alcohol use disorder and the dorsolateral striatum (DLS) is implicated in regulating this inflexible behavior. AMPA receptors have been implicated in both goal-directed (dorsomedial striatal dependent) and DLS dependent inflexible behaviors with antagonism in the DLS and general DLS inhibition altering inflexible behavior including habit and compulsion. Discrepancies exist in the preclinical models used to investigate compulsive-like alcohol. The purpose of these experiments was to establish a robust model of compulsive-like quinine adulterated alcohol (QuA) drinking in C57BL/6J male and female mice, assess associated AMPA receptor protein expression in the dorsal striatum, and to antagonize DLS AMPA receptors during compulsive-like QuA drinking using a model of binge-like alcohol drinking, Drinking-in-the-Dark (DID). Methods In aim 1, C57BL/6J mice were allowed free access to 20% (v/v) alcohol (alcohol history), or water (water history) for two hours each day beginning three hours into the dark cycle for 23 days. On days 15 and 22 mice were given QuA to test for compulsive-like QuA drinking. 24-hours following the last DID session brain slices were taking for DLS and DMS AMPA receptor western blot. In aim 2, C57BL/6J mice were given a total of 21 days alcohol history, to establish a compulsive-like phenotype, or water history, prior to infusion. On days 22 and 24 mice were given a bilateral infusion of one of three concentrations of NBQX, an AMPA receptor antagonist, into the DLS, immediately prior to DID where the DID solution was either alcohol or QuA. Results We found that three weeks, not two, is sufficient to produce robust compulsive-like QuA drinking in C57BL/6J mice. We failed to replicate our compulsive-like DID model in aim 2 and found that infusion of NBQX reduced 2-hour alcohol drinking and reduced 2-hour QuA drinking when QuA was the second solution presented on infusion days in male water history mice only. We also found that NBQX reduced 20-minute front-loading in female alcohol history mice on alcohol intake and trended toward QuA intake. Overall locomotor activity was affected by drug infusions. Conclusions Together, these data suggest that compulsive-like alcohol drinking can be achieved following three-weeks DID and DLS infusion of NBQX reduces both alcohol and QuA drinking in a sex and drinking history dependent way, and these effects may be reliant on an initial single QuA or alcohol exposure.Item Three Weeks of Binge Alcohol Drinking Generates Increased Alcohol Front-Loading and Robust Compulsive-Like Alcohol Drinking in Male and Female C57BL/6J Mice(Wiley, 2021-03) Bauer, Meredith R.; McVey, Megan M.; Boehm, Stephen L., II.; Psychology, School of ScienceBackground: 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.