Browsing by Author "McVey, Megan M."

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    Drinking history dependent functionality of the dorsolateral striatum on gating alcohol and quinine-adulterated alcohol front-loading and binge drinking
    (Elsevier, 2022) Bauer, Meredith R.; McVey, Megan M.; Boehm, Stephen L., II; Psychology, School of Science
    After an extended alcohol-drinking history, alcohol use can transition from controlled to compulsive, causing deleterious consequences. Alcohol use can be segregated into two distinct behaviors, alcohol seeking and alcohol taking. Expression of habitual and compulsive alcohol seeking depends on the dorsolateral striatum (DLS), a brain region thought to engage after extended alcohol access. However, it is unknown whether the DLS is also involved in compulsive-like alcohol taking. The purpose of this experiment was to identify whether the DLS gates compulsive-like binge alcohol drinking. To ask this question, we gave adult male and female C57BL/6J mice a binge-like alcohol-drinking history, which we have previously demonstrated to produce compulsive-like alcohol drinking (Bauer, McVey, & Boehm, 2021), or a water-drinking history. We then tested the involvement of the DLS on gating binge-like alcohol drinking and compulsive-like quinine-adulterated alcohol drinking via intra-DLS AMPA receptor antagonism. We hypothesized that pharmacological lesioning of the DLS would reduce compulsive-like quinine-adulterated alcohol (QuA) drinking, but not non-adulterated alcohol drinking, in male and female C57BL/6J mice. Three important findings were made. First, compulsive-like alcohol drinking is significantly blunted in cannulated mice. Because of this, we conclude that we were not able to adequately assess the effect of intra-DLS lesioning on compulsive-like alcohol drinking. Second, we found that the DLS gates binge-like alcohol drinking initially, which replicates findings in our previous work (Bauer, McVey, Germano, Zhang, & Boehm, 2022). However, following an extended alcohol history, the DLS no longer drives this behavior. Finally, alcohol and QuA front-loading is DLS-dependent in alcohol-history mice. Intra-DLS NBQX altered these drinking behaviors without altering ambulatory locomotor activity. These data demonstrate the necessity of the DLS in binge-like alcohol drinking before, but not following, an extended binge-like alcohol-drinking history and in alcohol front-loading in alcohol-history mice.
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    Intra-dorsolateral striatal AMPA receptor antagonism reduces binge-like alcohol drinking in male and female C57BL/6J mice
    (Elsevier, 2022) Bauer, Meredith R.; McVey, Megan M.; Germano, Damon M.; Zhang, Yanping; Boehm, Stephen L., II; Psychology, School of Science
    The dorsolateral striatum (DLS) is involved in addiction, reward, and alcohol related behaviors. The DLS primarily receives excitatory inputs which are gated by post-synaptic AMPA receptors. We antagonized AMPA receptors in the DLS to investigate how such modulation affects binge-like alcohol drinking in male and female C57BL/6J mice and whether an associated alcohol drinking history alters dorsomedial striatum (DMS) and DLS AMPA receptor expression. We also investigated the effect of intra-DLS NBQX on locomotor activity and saccharin drinking in mice. Mice were allowed free access to 20% alcohol for two hours each day for a total of seven days. Mice received an intra-DLS infusion of one of four concentrations of NBQX (saline, 0.15, 0.5, or 1.5 μg/side), an AMPA receptor antagonist, immediately prior to alcohol access on day 7. Two-hour binge alcohol intakes, locomotor activity, and blood alcohol concentrations were determined. Intra-DLS NBQX reduced binge-like alcohol drinking in a U-shaped manner in male and female mice. Intake predicted blood alcohol concentration, and locomotor activity was not affected. In a follow up experiment, we assessed whether the most effective NBQX concentration for reducing alcohol consumption also reduced saccharin drinking, finding intra-DLS NBQX did not alter saccharin drinking in male and female mice. These data suggest that AMPA receptors in the DLS play a role in the modulation of binge-like alcohol drinking. These findings further validate the importance of the DLS for alcohol related behaviors and alcohol use disorder.
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    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 Science
    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.