Alcohol is one of the most commonly abused drugs in the US, with 10% of the population affected by alcohol dependence at some point in their lives. An important newfocus is the development of new medications to help alcohol dependent patients reduce their alcohol use and promote abstinence. Potential targets for new medications are the multiple neurotransmitter systems of the brain reward systems including gamma- aminobutyric acid (GABA), glutamate, dopamine, cannabinoid and opioid peptides, which appear to be involved in the reinforcing effects of alcohol. Compulsive drinking can be conceptualized as a sequence of complex behaviors that terminate in alcohol consumption. Such complex sequences of behavior can be modeled in laboratory animals using chained schedules of reinforcement. The proposed studies will utilize a procedure in which initially neutral cues (lights and tones) are presented during 3 distinct components of a chained schedule of reinforcement. Each component is associated with an operant response requirement that is correlated with a distinct cue. Fulfilling the response requirement in the second component is necessary to progress to the third and final component. The primary reinforcer (alcohol or a preferred non- alcoholic beverage;Tang) will be available for self-administration only in the final component. This procedure allows the measurement of behaviors associated with alcohol anticipation, seeking, consumption and reinforcement within the same experimental session. The current proposal will evaluate the efficacyof newly proposed alcohol medications (e.g., topiramate, baclofen, 3-PBC and SR141716) in reducing alcohol seeking and consumption. In addition, current FDA-approved medications (naltrexone and acamprosate) will also be evaluated for comparison. The following hypotheses will be tested: 1) Test drugs will decrease alcohol self-administration behaviors and the amount of alcohol consumed, 2) Test drugs will decrease the motivation to gain access to alcohol, as measured by delaying onset of drinking and by reducing the maximum amount of work the subject will engage in to gain access to alcohol, 3) Decreases in self- administration and consumption produced by the test drugs will be greater for alcohol than for Tang, and 4) Test drugs will decrease the motivation to gain access to alcohol more than for Tang. These studies will provide important, previously unavailable, information on the differential behavioral efficacy of compounds that target receptor mechanisms believed to be influential in maintaining alcohol drinking and alcohol- seeking behaviors that are relevant to compulsive alcohol use and relapse in humans.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
Project #
Application #
Study Section
Neurotoxicology and Alcohol Study Section (NAL)
Program Officer
Egli, Mark
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
Schools of Medicine
United States
Zip Code
Holtyn, August F; Kaminski, Barbara J; Weerts, Elise M (2017) Baclofen and naltrexone effects on alcohol self-administration: Comparison of treatment initiated during abstinence or ongoing alcohol access in baboons. Drug Alcohol Depend 179:47-54
Holtyn, August F; Tiruveedhula, V V N Phani Babu; Stephen, Michael Rajesh et al. (2017) Effects of the benzodiazepine GABAA ?1-preferring antagonist 3-isopropoxy-?-carboline hydrochloride (3-ISOPBC) on alcohol seeking and self-administration in baboons. Drug Alcohol Depend 170:25-31
Lee, Mary R; Weerts, Elise M (2016) Oxytocin for the treatment of drug and alcohol use disorders. Behav Pharmacol 27:640-648
Kaminski, Barbara J; Weerts, Elise M (2014) The effects of varenicline on alcohol seeking and self-administration in baboons. Alcohol Clin Exp Res 38:376-83
Holtyn, August F; Kaminski, Barbara J; Wand, Gary S et al. (2014) Differences in extinction of cue-maintained conditioned responses associated with self-administration: alcohol versus a nonalcoholic reinforcer. Alcohol Clin Exp Res 38:2639-46
Duke, Angela N; Kaminski, Barbara J; Weerts, Elise M (2014) Baclofen effects on alcohol seeking, self-administration and extinction of seeking responses in a within-session design in baboons. Addict Biol 19:16-26
Kaminski, Barbara J; Van Linn, Michael L; Cook, James M et al. (2013) Effects of the benzodiazepine GABAA ?1-preferring ligand, 3-propoxy-?-carboline hydrochloride (3-PBC), on alcohol seeking and self-administration in baboons. Psychopharmacology (Berl) 227:127-36
Kaminski, Barbara J; Duke, Angela N; Weerts, Elise M (2012) Effects of naltrexone on alcohol drinking patterns and extinction of alcohol seeking in baboons. Psychopharmacology (Berl) 223:55-66
Kaminski, Barbara J; Goodwin, Amy K; Wand, Gary et al. (2008) Dissociation of alcohol-seeking and consumption under a chained schedule of oral alcohol reinforcement in baboons. Alcohol Clin Exp Res 32:1014-22