Corticostriatal processing of alcohol-paired cues in aversion-resistant drinking (CAPD) Treatment resistant alcoholism is characterized by a loss of control over drinking where individuals persistently use in spite of negative consequences. Currently approved treatments for alcoholism (e.g. disulfiram) aim to reduce drinking by making alcohol consumption aversive. However, this approach is problematic as the hedonic properties of alcohol may no longer motivate drinking behavior in advanced stages of the disease. Rather, when drinking has advanced to a stage that is resistant to aversive consequences, the control of behavior is thought to transition from neural circuits that mediate higher cognitive functions to those that mediate compulsions and habits. Two prominent factors that influence the transition to this stage of drinking are history of alcohol use and genetic risk for alcohol abuse (e.g. family history). Preliminary data from Indiana Alcohol Research Center (IARC) investigators demonstrate that certain rodent models of genetic risk for excessive drinking also tend to quickly form habits and compulsive behaviors. Therefore, a critical need exists to understand how alcohol exposure and genetic factors influence the computational properties of brain regions necessary for the cognitive control of motivated behavior. The long-term goal of this project is to understand the heritable changes in neural computation that facilitate the transition to a loss of control over drinking. Following this transition, alcohol associated cues retain extreme incentive motivational properties even when associated with aversive consequences. A method commonly used to assess aversion resistant drinking (ARD) in rodents is measuring their willingness to consume alcohol adulterated with a bad taste - the quinine devaluation procedure. The central hypothesis of this proposal is that the genetic predisposition to allocate cognitive resources in a stimulus-dependent manner interacts with chronic alcohol use to facilitate ARD. Electrophysiological recordings will be obtained from the medial prefrontal cortex and ventral striatum of awake behaving alcohol preferring (P) and Wistars rats performing a Pavlovian cued access drinking procedure. This approach will allow the representation of alcohol-paired cues to be measured at the individual neuron and ensemble levels to determine how they are processed differently during ARD. Rigorous statistical procedures will be use to quantify the representation of alcohol-paired cues in corticostriatal circuits, and how they are influenced by alcohol history and genetic risk.
Aim 1 will examine changes in the representation of alcohol-paired cues following alcohol exposure to determine if drinking history and genetic risk enhances the encoding of alcohol-paired cues in corticostriatal circuits.
Aim 2 will determine if drinking history and genetic risk impair the ability of corticostriatal circuits to remap representations of alcohol-paired cues. Finally, Aim 3 will determine if drinking history and genetic risk enhance corticostriatal representations of alcohol-paired cues in Aversion-Resistant Drinking. These data will shed light on the changes in corticostriatal function that underlie ARD, and are therefore consistent with the overarching goals of the IARC.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Comprehensive Center (P60)
Project #
5P60AA007611-33
Application #
9828761
Study Section
Special Emphasis Panel (ZAA1)
Project Start
Project End
Budget Start
2019-12-01
Budget End
2020-11-30
Support Year
33
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Type
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Weera, Marcus M; Agim, Zeynep S; Cannon, Jason R et al. (2018) Genetic correlations between nicotine reinforcement-related behaviors and propensity toward high or low alcohol preference in two replicate mouse lines. Genes Brain Behav :e12515
Oberlin, Brandon G; Dzemidzic, Mario; Eiler 2nd, William J A et al. (2018) Pairing neutral cues with alcohol intoxication: new findings in executive and attention networks. Psychopharmacology (Berl) 235:2725-2737
Chumin, Evgeny J; Goñi, Joaquín; Halcomb, Meredith E et al. (2018) Differences in White Matter Microstructure and Connectivity in Nontreatment-Seeking Individuals with Alcohol Use Disorder. Alcohol Clin Exp Res 42:889-896
Eiler 2nd, William J A; Dzemidzic, Mario; Soeurt, Christina M et al. (2018) Family history of alcoholism and the human brain response to oral sucrose. Neuroimage Clin 17:1036-1046
Weafer, Jessica; Ross, Thomas J; O'Connor, Sean et al. (2018) Striatal activity correlates with stimulant-like effects of alcohol in healthy volunteers. Neuropsychopharmacology 43:2532-2538
Weera, Marcus M; Fields, Molly A; Tapp, Danielle N et al. (2018) Effects of Nicotine on Alcohol Drinking in Female Mice Selectively Bred for High or Low Alcohol Preference. Alcohol Clin Exp Res 42:432-443
Gerke, Steven P; Agley, Jon D; Wilson, Cynthia et al. (2018) An Initial Assessment of the Utility of Validated Alcohol and Drug Screening Tools in Predicting 30-Day Readmission to Adult General Medicine Wards. Am J Med Qual 33:397-404
Bujarski, Spencer; Jentsch, J David; Roche, Daniel J O et al. (2018) Differences in the subjective and motivational properties of alcohol across alcohol use severity: application of a novel translational human laboratory paradigm. Neuropsychopharmacology 43:1891-1899
Plawecki, Martin Henry; White, Kurt; Kosobud, Ann E K et al. (2018) Sex Differences in Motivation to Self-Administer Alcohol After 2 Weeks of Abstinence in Young-Adult Heavy Drinkers. Alcohol Clin Exp Res 42:1897-1908
Plawecki, Martin H; Windisch, Kyle A; Wetherill, Leah et al. (2018) Alcohol affects the P3 component of an adaptive stop signal task ERP. Alcohol 70:1-10

Showing the most recent 10 out of 308 publications