Browsing by Subject "Binge"

Now showing 1 - 6 of 6
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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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    Rodent models and mechanisms of voluntary binge-like ethanol consumption: Examples, opportunities, and strategies for preclinical research
    (Elsevier, 2016-02-04) Fritz, Brandon M.; Boehm II, Stephen L.; Department of Psychology, School of Science
    Binge ethanol consumption has widespread negative consequences for global public health. Rodent models offer exceptional power to explore the neurobiology underlying and affected by binge-like drinking as well as target potential prevention, intervention, and treatment strategies. An important characteristic of these models is their ability to consistently produce pharmacologically-relevant blood ethanol concentration. This review examines the current available rodent models of voluntary, pre-dependent binge-like ethanol consumption and their utility in various research strategies. Studies have demonstrated that a diverse array of neurotransmitters regulate binge-like drinking, resembling some findings from other drinking models. Furthermore, repeated binge-like drinking recruits neuroadaptive mechanisms in mesolimbocortical reward circuitry. New opportunities that these models offer in the current context of mechanistic research are also discussed.
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    Sex-dependent, lateralized engagement of anterior insular cortex inputs to the dorsolateral striatum in binge alcohol drinking
    (eLife Sciences, 2024-08-28) Haggerty, David L.; Atwood, Brady K.; Pharmacology and Toxicology, School of Medicine
    How does alcohol consumption alter synaptic transmission across time, and do these alcohol-induced neuroadaptations occur similarly in both male and female mice? Previously we identified that anterior insular cortex (AIC) projections to the dorsolateral striatum (DLS) are uniquely sensitive to alcohol-induced neuroadaptations in male, but not female mice, and play a role in governing binge alcohol consumption in male mice (Haggerty et al., 2022). Here, by using high-resolution behavior data paired with in-vivo fiber photometry, we show how similar levels of alcohol intake are achieved via different behavioral strategies across sexes, and how inter-drinking session thirst states predict future alcohol intakes in females, but not males. Furthermore, we show how presynaptic calcium activity recorded from AIC synaptic inputs in the DLS across 3 weeks of water consumption followed by 3 weeks of binge alcohol consumption changes across, fluid, time, sex, and brain circuit lateralization. By time-locking presynaptic calcium activity from AIC inputs to the DLS to peri-initiation of drinking events we also show that AIC inputs into the left DLS robustly encode binge alcohol intake behaviors relative to water consumption. These findings suggest a fluid-, sex-, and lateralization-dependent role for the engagement of AIC inputs into the DLS that encode binge alcohol consumption behaviors and further contextualize alcohol-induced neuroadaptations at AIC inputs to the DLS.
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    Systemic administration of racemic baclofen reduces both acquisition and maintenance of alcohol consumption in male and female mice
    (Elsevier, 2022) Bauer, Meredith R.; Hernández, Maribel; Kasten, Chelsea R.; Boehm, Stephen L., II; Psychology, School of Science
    Baclofen is a GABAB receptor agonist with proposed use as a treatment for alcohol use disorder (AUD). In preclinical studies, racemic baclofen decreases alcohol consumption in both mice and rats; however, there is a significant disparity in the efficacy of the drug across species. We previously demonstrated that baclofen is enantioselective, with the racemic enantiomer successfully reducing binge-like alcohol consumption during Drinking-in-the-Dark (DID) in C57BL/6J (B6) mice, as well as 24-h consumption during two-bottle choice (2BC) preference drinking in replicate 1 High Alcohol Preferring (HAP) mice. Here we extend these findings by investigating the effects of racemic baclofen on the acquisition and maintenance of alcohol consumption, locomotor activity, and saccharin drinking in two different mouse genotypes and drinking paradigms. Adult male and female B6 mice were allowed free access to 20% (v/v) alcohol for 2 h daily in a 14-day DID procedure. Adult male and female replicate 2 HAP (HAP2) mice were allowed 24-h access to 10% (v/v) alcohol versus tap water in a 2BC procedure for 14 days. Systemic injections of baclofen (0.0 or 3.0 mg/kg) were given 3 h into the dark cycle on days 1–5 in alcohol acquisition experiments and days 6–10 in alcohol maintenance experiments. We found that racemic baclofen significantly reduces acquisition of DID and 2BC alcohol drinking in male and female B6 and HAP2 mice, whereas it only significantly reduces the maintenance of DID alcohol intake in B6 mice. Racemic baclofen did not alter home cage locomotor activity but did alter saccharin intake, suggesting it may have nonspecific effects. The current data add to literature suggesting that smaller doses of racemic baclofen may be an effective treatment of AUD. Future work should focus on the longitudinal efficacy of racemic baclofen in high-drinking mouse genotypes to further investigate whether it is effective for those with a genetic predisposition to AUD.
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    Systemic Administration of the AMPA Receptor Antagonist, NBQX, Reduces Alcohol Drinking in Male C57BL/6J, but not Female C57BL/6J or High Alcohol Preferring (HAP) Mice
    (Wiley, 2020-11) Bauer, Meredith R.; Garcy, Daniel P.; Boehm, Stephen L., II.; Psychology, School of Science
    Background: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are ionotropic glutamate receptors that have been investigated for their role in modulating alcohol consumption. However, little is known about the role of AMPA receptors in the control of binge-like or free-access alcohol drinking in C57BL/6J or in selectively bred high-alcohol-preferring (HAP) mice. The purpose of this experiment was to assess the role of systemic administration of the AMPA receptor antagonist, 2,3-dioxo-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX), on alcohol consumption using a model of binge-like drinking, drinking in the dark (DID) and free-access 2-bottle choice (2BC) in male and female C57BL/6J and HAP mice. Methods: C57BL/6J mice were allowed free access to 20% (v/v) alcohol for 2 hours each day beginning 3 hours into the dark cycle for 4 days. On day 5, mice were intraperitoneally injected with one of 4 doses of NBQX (0, 3, 10, or 30 mg/kg; n = 10) 15 minutes before alcohol presentation and were given 4-hour alcohol access (extended DID). HAP mice were given 24-hour free access to 10% (v/v) alcohol and water for 19 days. On day 20, mice were intraperitoneally injected with one of 4 doses of NBQX (0, 3, 10, or 30 mg/kg; n = 9) 15 minutes before alcohol and water presentation. Results: In the first 2 hours of DID, at 30 mg/kg, male, but not female C57BL/6J or HAP, mice drank significantly less alcohol compared with controls and 30 mg/kg NBQX did not alter saccharin intake in the males. Although male HAP mice drank significantly less alcohol than female mice following 10 mg/kg NBQX, neither sex exhibited drinking that differed significantly from controls. NBQX did not reduce locomotor behavior at any dose, sex, or genotype. Conclusions: These data suggest that AMPA receptors play a key role in modulating binge-like alcohol consumption without altering saccharin consumption or general locomotion and that this effect is specific to sex and genotype.
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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.