High rates of relapse to drug use after long periods of abstinence characterize the behavior of experienced users of alcohol. An important factor for provoking relapse to alcohol in humans is exposure to stress. However, until recently a preclinical model to study this phenomenon under controlled experimental conditions did not exist. We have developed a reinstatement procedure to study the effect of exposure to stress on relapse to alcohol seeking in alcohol-experienced rats that are drug-free at the time of testing. In the reinstatement procedure, the ability of acute exposure to drug or non-drug stimuli to reinstate drug seeking is examined after training for drug self-administration and subsequent extinction of the drug-reinforced behavior. We have shown that brief exposure to intermittent footshock stress potently reinstates alcohol seeking in alcohol-experienced rats that are drug-free at the time of tests for relapse. These data provide the first preclinical demonstration of stress-induced relapse to alcohol seeking. Subsequently, we have found that the serotonin reuptake blocker, fluoxetine, and corticotropin-releasing factor (CRF) receptor antagonists attenuate stress-induced relapse to alcohol. On the basis of these findings, we now propose to further characterize neurochemical and environmental events involved in relapse to alcohol induced by stressors. Characterization of the relapse process in our preclinical model may lead to the development of medications for relapse prevention in humans.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
1R01AA013108-01A1
Application #
6424589
Study Section
Alcohol and Toxicology Subcommittee 4 (ALTX)
Program Officer
Egli, Mark
Project Start
2002-04-01
Project End
2006-03-31
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
1
Fiscal Year
2002
Total Cost
$140,400
Indirect Cost
Name
Centre for Addiction and Mental Health
Department
Type
DUNS #
City
Toronto
State
ON
Country
Canada
Zip Code
M5S2S-1
Funk, D; Lo, S; Coen, K et al. (2016) Effects of varenicline on operant self-administration of alcohol and/or nicotine in a rat model of co-abuse. Behav Brain Res 296:157-162
Lê, A D; Funk, Douglas; Lo, Steven et al. (2014) Operant self-administration of alcohol and nicotine in a preclinical model of co-abuse. Psychopharmacology (Berl) 231:4019-29
Zou, Sheng; Funk, Douglas; Shram, Megan J et al. (2014) Effects of stressors on the reinforcing efficacy of nicotine in adolescent and adult rats. Psychopharmacology (Berl) 231:1601-14
Funk, Douglas; Coen, Kathleen; Lê, A D (2014) The role of kappa opioid receptors in stress-induced reinstatement of alcohol seeking in rats. Brain Behav 4:356-67
Grella, Stephanie L; Funk, Douglas; Coen, Kathy et al. (2014) Role of the kappa-opioid receptor system in stress-induced reinstatement of nicotine seeking in rats. Behav Brain Res 265:188-97
Li, Sophia; Zou, Sheng; Coen, Kathleen et al. (2014) Sex differences in yohimbine-induced increases in the reinforcing efficacy of nicotine in adolescent rats. Addict Biol 19:156-64
Le, A D; Funk, Douglas; Coen, Kathleen et al. (2013) Role of corticotropin-releasing factor in the median raphe nucleus in yohimbine-induced reinstatement of alcohol seeking in rats. Addict Biol 18:448-51
Lê, A D; Funk, Douglas; Juzytsch, Walter et al. (2011) Effect of prazosin and guanfacine on stress-induced reinstatement of alcohol and food seeking in rats. Psychopharmacology (Berl) 218:89-99
Le, A D; Lo, Steven; Harding, Stephen et al. (2010) Coadministration of intravenous nicotine and oral alcohol in rats. Psychopharmacology (Berl) 208:475-86
Marinelli, Peter W; Funk, Douglas; Juzytsch, Walter et al. (2010) Opioid receptors in the basolateral amygdala but not dorsal hippocampus mediate context-induced alcohol seeking. Behav Brain Res 211:58-63

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