The proposed work innovatively addresses serious and long-standing limitations in the evidence supporting the standard relapse model. The important role of the standard model both in pre-clinical research into relapse and in clinical treatments to prevent relapse make it important to strongly test the assumptions of the standard model. This work could result in a strong validation of the standard model and improved animal models for developing medications designed to prevent relapse and craving. Alternatively, this work might indicate that other, less understood, behavioral mechanisms are at play and redirect our efforts towards identifying and understanding the behavioral biology of these mechanisms;and developing new more effective treatments based upon this improved understanding. Finally, this work extends the study of the role of classical conditioning from relapse to recovery, an extension that may aid in the development of new and different approaches to the treatment of problem drinking. While a substantial body of evidence indicates that Ethanol-Paired-Stimuli (EPS) increase ethanol-seeking (in animals) and increase craving (in humans), little evidence is available to show that this increased ethanol- seeking (or craving) is the result of an EPS serving as a CS. Additionally, linking our pre-clinical measure of craving (increased ethanol-seeking) to the actual clinical phenomenon of craving is difficult. Further, this EPS occasioned increase in ethanol-seeking (or craving) has not been shown to result in increased drinking.
AIM I of this proposal would examine whether an EPS can increase ethanol-seeking by functioning as a CS, whether this increased ethanol-seeking actually results in increased drinking (and other relapse-like behaviors), and AIM II begins to assess whether an EPS can produce craving-like effects in rats by acting as a CS. This work could result in strong validation of the standard model and improved animal models for developing medications to prevent relapse and craving. Alternatively, this work may indicate that other, less understood, behavioral mechanisms are at work and redirect our efforts towards identifying and under- standing the behavioral biology of these mechanisms;and developing new more effective treatments based upon this improved understanding. Finally, the role of classical conditioning and associative learning in problem drinking almost certainly extends beyond their role in relapse.
AIM III begins to address these other roles by examining the role associative learning may play in recovery. By developing animal models of recovery, this project develops new tools for the development of better treatments of problem drinking.

Public Health Relevance

Clinical research in alcoholism has focused largely on how stimuli paired with alcohol consumption might nudge behavior towards dangerous levels of alcohol consumption, while pre-clinical research has focused more on how the consumption of alcohol traps alcohol-seeking behavior to increase the future probability of alcohol- seeking. In this translational pre-clinical research, we propose to examine how alcohol-paired stimuli might nudge alcohol-seeking so that it becomes trapped by its consequences.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
2R01AA012337-11A1
Application #
8761716
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Egli, Mark
Project Start
2001-09-24
Project End
2017-07-31
Budget Start
2014-08-10
Budget End
2015-07-31
Support Year
11
Fiscal Year
2014
Total Cost
$336,375
Indirect Cost
$111,375
Name
University of Texas Health Science Center
Department
Psychiatry
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Ginsburg, Brett C; Lamb, Richard J (2014) Relative potency of varenicline or fluvoxamine to reduce responding for ethanol versus food depends on the presence or absence of concurrently earned food. Alcohol Clin Exp Res 38:860-70
Pinkston, Jonathan W; Ginsburg, Brett C; Lamb, Richard J (2014) Reinforcer magnitude and rate dependency: evaluation of resistance-to-change mechanisms. Behav Pharmacol 25:629-36
Ginsburg, B C; Lamb, R J (2014) Drug effects on multiple and concurrent schedules of ethanol- and food-maintained behaviour: context-dependent selectivity. Br J Pharmacol 171:3499-510
Lamb, R J; Daws, L C (2013) Ethanol self-administration in serotonin transporter knockout mice: unconstrained demand and elasticity. Genes Brain Behav 12:741-7
Ginsburg, Brett C; Lamb, R J (2013) A history of alternative reinforcement reduces stimulus generalization of ethanol-seeking in a rat recovery model. Drug Alcohol Depend 129:94-101
Romanowich, Paul; Lamb, R J (2013) The effects of chlordiazepoxide and d-amphetamine during a three-component multiple schedule. J Exp Anal Behav 100:88-101
Ginsburg, Brett C; Lamb, R J (2013) Reinforcement of an alternative behavior as a model of recovery and relapse in the rat. Behav Processes 94:60-6
Ginsburg, Brett C; Lamb, Richard J (2013) Effects of varenicline on ethanol- and food-maintained responding in a concurrent access procedure. Alcohol Clin Exp Res 37:1228-33
Ginsburg, Brett C; Pinkston, Jonathan W; Lamb, Richard J (2012) The potency of fluvoxamine to reduce ethanol self-administration decreases with concurrent availability of food. Behav Pharmacol 23:134-42
Pinkston, Jonathan W; Lamb, R J (2011) Delay discounting in C57BL/6J and DBA/2J mice: adolescent-limited and life-persistent patterns of impulsivity. Behav Neurosci 125:194-201

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