Browsing by Subject "compulsive"

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    Assessing Motivational and Associative Learning Mechanisms Underlying Compulsive Drinking
    (2021-08) Carron, Claire R.; Grahame, Nicholas; Czachowski, Cristine; Lapish, Christopher; Hopf, Fredric
    Continued consumption of alcohol despite the knowledge of negative consequences is a hallmark of alcohol use disorder (AUD), yet much remains unknown about what motivates these behaviors. Compulsive drinking may require motivational resources that are not necessary when drinking in unchallenged conditions in order to counteract the addition of these negative consequences. Increased sensitivity to drug-paired stimuli via associative learning processes may provide this additional motivation. To evaluate if alcohol-paired stimuli enhance alcohol seeking, selectively bred crossed High Alcohol Preferring mice experienced Pavlovian conditioning procedures with an alcohol unconditioned stimulus. We hypothesized that after repeated pairings, alcohol cues would elicit seeking conditioned responses. Then, to determine if the motivation provided by these cues influenced responding, mice were trained to respond for alcohol and tested in the presence of alcohol cues. Finally, to test if alcohol-paired cues influence compulsive drinking, this same test was repeated with the addition of response-contingent footshock. We hypothesized the cue paired with alcohol would increase responding for alcohol in unchallenged conditions, but especially in challenged conditions, contributing to compulsivity. An auditory stimulus paired with alcohol did elicit enhanced seeking responses, but contrary to hypothesis, we observed no effect of these same cues on instrumental responding. To validate these findings, training and testing procedures must be optimized to ensure conditioning has properly occurred and compulsivity is being appropriately measured.
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    Role of the Prefrontal Cortex to Dorsomedial Striatum Projections in Compulsive Alcohol Drinking
    (2023-12) Bauer, Meredith; Boehm, Stephen; Lapish, Christopher; Grahame, Nicholas; Gremel, Christina
    Compulsive alcohol drinking is a defining feature of alcohol use disorder and is characterized as drinking alcohol despite knowledge of negative consequences. This behavior is hypothesized to be due to a disruption in the decision-making process. Decision making relies on a balance between goal-directedness and habit systems to efficiently execute behavior. An important distinction between compulsive and non-compulsive individuals is the ability to withhold drinking in the face of a negative consequence. The dorsomedial striatum (DMS) and dorsomedial prefrontal cortex (dmPFC) are brain regions necessary for goal directed behavior where the dmPFC is important for cognitive control and behavioral inhibition while the DMS is important for action selection. Importantly, the dmPFC sends a glutamatergic input to the DMS. We hypothesize this input is a behavioral control which is necessary to withhold action selection. Thus, in order to maintain non-compulsive alcohol use, the dmPFC and DMS need to work together to orchestrate inhibition of action selection in the face of negative consequences. Previous research shows a causal role for both the dmPFC and DMS in preventing compulsive alcohol drinking and a role for the projections from the dmPFC to DMS in behavioral inhibition. However, no research has demonstrated a role for this circuit’s activity in prevention of compulsive alcohol use. The current experiment tested the hypothesis that inhibiting the glutamatergic projection from the dmPFC to the DMS will cause non-compulsive Wistar rats to drink alcohol compulsively.