The goal of the proposed research is to understand the effects of ethanol exposure on neural systems responsible for the control of goal-directed actions and habit formation. Ethanol addiction is associated with a wide range of behavioral and cognitive deficits. While much progress has been made on the pharmacological targets mediating ethanol action on the brain, little is known about the adaptations resulting from ethanol addiction at the level of neural systems. So far, the majority of research on the effects of ethanol on goal-directed behavior has focused on alcohol self-administration paradigms. Rather neglected is the question of how ethanol affects the neural systems underlying normal reward-guided behavior. To understand the neuroadapative mechanisms responsible for the addictive properties of ethanol, we must first understand how it affects the normal mechanisms underlying reward-guided behavior in general. More specifically, little research has been conducted on the effects of ethanol on the striatum, a key structure in the control of voluntary behavior that has been implicated in habit formation and addiction as a result of recent research. Consequently, not much is known about how ethanol can change striatum-dependent learning and behavior. In this proposal it is hypothesized that exposure to ethanol (using the ethanol vapor chamber procedure) can usurp normal learning processes in the striatum that are engaged in automatization of skills and habit formation to have significant impact on the subsequent control of reward- guided behavior. Accordingly, three specific aims are proposed: 1) To determine the effects of prior ethanol exposure on striatum-dependent learning and behavior. 2) To determine the effects of prior ethanol exposure on striatal neural activity in awake behaving mice during instrumental learning. 3) To determine the effects of prior ethanol exposure on striatal synaptic transmission ex vivo using whole-cell patch clamp recording. This proposal employs an innovative and integrative approach in studying ethanol actions on the brain, by combining in vivo and ex vivo electrophysiological methods with powerful assays from the study of instrumental learning. Results from the proposed experiments will help us understand the neuroadaptive mechanisms in the cortico-striatal circuits that mediate the acquisition and control of goal-directed actions and habit formation. Such mechanisms can provide novel targets for the treatment of alcohol addiction.

Public Health Relevance

Recent work has suggested a critical role for the dorsal striatum in habit formation. As a consequence, the involvement of different striatal regions in addiction is now becoming a focus of research. However, it is not clear how alcohol affects the neural circuits underlying habit formation. Results from the proposed studies will significantly advance our understanding of how exposure to alcohol can usurp plasticity mechanisms normally engaged in habit formation to promote to alter the control of voluntary behavior. Such knowledge can potentially lead to better treatment options that are specifically targeted at the physiological processes responsible for the development of habitual and compulsive alcohol seeking behavior.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAA1-CC (02))
Program Officer
Liu, Qi-Ying
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Duke University
Schools of Arts and Sciences
United States
Zip Code
Rossi, Mark A; Yin, Henry H (2012) Methods for studying habitual behavior in mice. Curr Protoc Neurosci Chapter 8:Unit 8.29
Derusso, Alicia L; Fan, David; Gupta, Jay et al. (2010) Instrumental uncertainty as a determinant of behavior under interval schedules of reinforcement. Front Integr Neurosci 4:
Yin, Henry H (2010) The sensorimotor striatum is necessary for serial order learning. J Neurosci 30:14719-23
Yu, Chunxiu; Gupta, Jay; Chen, Jiang-Fan et al. (2009) Genetic deletion of A2A adenosine receptors in the striatum selectively impairs habit formation. J Neurosci 29:15100-3