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Neural Basis of Chronic and Binge Al...

Starski, Phillip Anthony.

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Neural Basis of Chronic and Binge Alcohol Exposure and Impulsive Behaviors.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Neural Basis of Chronic and Binge Alcohol Exposure and Impulsive Behaviors./
作者:	Starski, Phillip Anthony.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2020,
面頁冊數:	277 p.
附註:	Source: Dissertations Abstracts International, Volume: 81-10, Section: B.
Contained By:	Dissertations Abstracts International81-10B.
標題:	Neurosciences. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=27831298
ISBN:	9798607318673

Neural Basis of Chronic and Binge Alcohol Exposure and Impulsive Behaviors.
Starski, Phillip Anthony.

Neural Basis of Chronic and Binge Alcohol Exposure and Impulsive Behaviors. - Ann Arbor : ProQuest Dissertations & Theses, 2020 - 277 p.

Source: Dissertations Abstracts International, Volume: 81-10, Section: B.

Thesis (Ph.D.)--College of Medicine - Mayo Clinic, 2020.

This item must not be sold to any third party vendors.

Impulsivity is a risk factor for many psychiatric disorders including alcohol use disorder (AUD). Highly impulsive individuals are more vulnerable to alcohol abuse due to increased risk taking behaviors. However, it is not well understood whether binge alcohol use increases the propensity for impulsive behavior and its effect on the anterior cingulate cortex (ACC), a main brain region encoding impulsivity. In this study, we utilized a novel experimental paradigm demonstrating that binge-like ethanol exposure progressively leads to maladaptive impulsive behavior. For testing waiting impulsivity, we employed the 5-choice serial reaction time task (5-CSRTT) in C57BL/6J male mice, a task strongly correlated with the anterior cingulate cortex. We assessed premature responses during reward seeking in fixed and variable inter-trial interval (ITI) 5-CSRTT sessions. We further characterized our ethanol-induced impulsive mice using the open field, y-maze, 2-bottle choice, and an action-outcome task. Finally, we performed label-free proteomic analysis of the ACC to observe protein changes in ethanol-induced impulsive mice compared to untreated mice. Our results demonstrated that binge-like ethanol exposure significantly increased premature responses during variable ITI sessions during a prolonged abstinent period. Ethanol treated mice exhibited anxiety-like behavior during their impulsivity testing and was observed again after twenty days of treatment abstinence. Ethanol treated mice were displaying signs of anhedonia through decreased motivation for a sucrose reward compared to air-exposed control mice, while also demonstrating reduced responses during devaluation testing.Next, ingenuity pathway analysis revealed a significant change of several impulsivity-related proteins such as KCNIP3 (potassium voltage-gated channel interacting protein 3) and CACNG2 (calcium voltage-gated channel subunit gamma 2). Furthermore, ingenuity pathway analysis showed that mTOR (mechanistic target of rapamycin) canonical pathway to be highly affected in ethanol-induced impulsive mice compared to control mice. Overall, our findings indicate that ethanol treated mice increased impulsive behavior, but reduced hedonic behavior for the sucrose reward. Proteomic profiles of ethanol-induced impulsive mice may explain molecular mechanisms underpinning maladaptive impulsive behavior. Further, we replicated our ethanol exposure paradigm in order to utilize inhibitory DREADD (Designer Receptors Exclusively Activated by Designer Drugs) chemogenetics to attenuate maladaptive impulsivity. We injected a AAV5-CaMKII-hM4Di-mCherry virus into the prelimbic area of the medial prefrontal cortex of ethanol and air exposed mice. Thirty minutes prior to 5-CSRTT testing, mice were given 3 mg/kg of the receptor activating ligand clozapine-N-oxide. Mice experiencing increased waiting impulsivity due to the ethanol exposure decreased their premature response rate to similar levels as the control mice. Our result suggests that the prelimbic cortex is an important mediator of maladaptive impulse control caused by ethanol.

ISBN: 9798607318673Subjects--Topical Terms:

588700
Neurosciences.
Subjects--Index Terms:

5CSRTT

Neural Basis of Chronic and Binge Alcohol Exposure and Impulsive Behaviors.
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