Alcoholism is a chronic disorder, typically spanning several decades. The learning processes underlying habit formation may contribute to continued alcohol drinking and render the behavior resistant to change. The degree to which habits (actions driven by conditioned cues and independent of outcome) versus goal-directed behaviors (actions dependent on the outcome or drug) drive alcohol drinking may influence susceptibility to relapse. Operant conditioning paradigms in rats, which can produce robust goal-directed or habitual behavior, can model the contribution of habit to alcohol drinking and allow direct measurement of brain function during these behaviors. The dorsomedial striatum (DMS) underlies goal-directed behavior while the dorsolateral striatum (DLS) is crucial for habit formation, and both areas are involved in animal models of relapse. Dopamine input is essential to the association between cues and drugs, and has profound and region-specific effects on synaptic plasticity, neuronal activity and behavior. The critical dopamine signal in cue-action habits may be fast changes in dopamine (or transients) that can occur in response to salient stimuli and that can only be measured with fast scan cyclic voltammetry. In addition, medium spiny neurons in the dorsal striatum can encode reward-related cues and actions by short-term changes in firing rates, which may be dopamine- dependent. This proposal will test the overall hypothesis that subsecond dopamine release and ongoing neuronal activity differ in DMS versus DLS, with the DMS preferentially active during goal-directed alcohol reinforcement, and the DLS preferentially active during habitual alcohol reinforcement and cue-induced relapse. We will use state-of-the-art, real-time recording techniques in rats: fast scan cyclic voltammetry to reveal dopamine transients, and extracellular recording at multielectrode arrays to evaluate ensemble activity of MSNs. Moreover, we will make this combination of chemical and physiological measurements during goal- directed and habitual alcohol drinking (Aims 1 and 2) as well as relapse-like behavior (Aims 3 and 4), to provide the most complete picture to date of dorsal striatal encoding of alcohol-related habit formation. Mechanistic studies will investigate the functional role of dopamine release in the physiological events associated with habitual drinking and relapse. The data resulting from these innovative studies will provide important information about how the dorsal striatum differentially encodes goal-directed versus habitual alcohol drinking. Overall, these studies have the potential to identify novel mechanisms by which habitual alcohol drinking leads to changes in brain and behavioral processes that are of fundamental importance to both the development and treatment of alcohol abuse and alcoholism.

Public Health Relevance

Habitual alcohol drinking and cue-induced relapse are major factors to alcoholism. We will examine dopamine release and neural activity in rat models of habitual alcohol drinking and cue-induced relapse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA018008-05
Application #
8314143
Study Section
Special Emphasis Panel (ZAA1-CC (02))
Program Officer
Liu, Qi-Ying
Project Start
2008-09-30
Project End
2013-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
5
Fiscal Year
2012
Total Cost
$299,274
Indirect Cost
$97,062
Name
University of North Carolina Chapel Hill
Department
Psychiatry
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599