There is increasing evidence that the endogenous opiate and serotonin systems are involved in the experience of alcohol effects and in the maintenance of alcohol consumption. The opiate antagonist drug, naltrexone, and the serotonin receptor type 3 antagonist drug, ondansetron, have reported utility in reducing alcohol consumption in animals and man. Despite strong evidence of the clinical efficacy of naltrexone, not everyone benefits, and relapse is common. Similar to poly-etiologic conditions such as hypertension and cancer, it would make sense to combine drugs of different actions to enhance alcoholism treatment effectiveness. While prospective treatment trials in alcoholism are the only definitive method for evaluating the utility of medications for the treatment of this condition, these trials are costly, time consuming, and with chronic exposure, put patients at risk for adverse effects. We propose to examine the combined effects of naltrexone and ondansetron on alcohol reactivity in an acute paradigm as a first step toward understanding the potential efficacy of combining these medications in clinical trials. The proposed study will be a randomized placebo controlled comparison of the ability of naltrexone, ondansetron or their combination, to alter alcohol consumption and reactivity utilizing 1) natural observation 2) alcohol cue brain imaging 3) an acute administration of alcohol and 4) consumption of alcohol in a limited-access paradigm. Non-treatment seeking alcoholics (N=160) and social drinkers (N=16 as procedure controls) will be randomly assigned to take placebo, naltrexone, ondansetron or the combination for 8 days. A subset of individuals in each medication group will participate in an alcohol cue brain imaging (fMRI) paradigm on day seven. On the eight day all subjects will ingest a fixed dose of the beverage of their choice followed by a limited-cell alcohol consumption period. Regional brain activity changes (cue stimulation), alcohol stimulation (pharmacological), and motivated consumption (cognitive control and craving) will be assessed. Subjects will be paid for their participation and alcoholic individuals will undergo a brief motivation counseling session at the end of the protocol to educate them about the risk of heavy alcohol consumption and motivate them to reduce drinking or seek treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Specialized Center (P50)
Project #
3P50AA010761-07S1
Application #
6655143
Study Section
Special Emphasis Panel (ZAA1)
Project Start
2002-09-01
Project End
2002-12-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
7
Fiscal Year
2002
Total Cost
$242,857
Indirect Cost
Name
Medical University of South Carolina
Department
Type
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
McGuier, Natalie S; Rinker, Jennifer A; Cannady, Reginald et al. (2018) Identification and validation of midbrain Kcnq4 regulation of heavy alcohol consumption in rodents. Neuropharmacology 138:10-19
Nimitvilai, Sudarat; Lopez, Marcelo F; Woodward, John J (2018) Effects of monoamines on the intrinsic excitability of lateral orbitofrontal cortex neurons in alcohol-dependent and non-dependent female mice. Neuropharmacology 137:1-12
Dowdle, Logan T; Brown, Truman R; George, Mark S et al. (2018) Single pulse TMS to the DLPFC, compared to a matched sham control, induces a direct, causal increase in caudate, cingulate, and thalamic BOLD signal. Brain Stimul 11:789-796
Zamudio-Bulcock, Paula A; Homanics, Gregg E; Woodward, John J (2018) Loss of Ethanol Inhibition of N-Methyl-D-Aspartate Receptor-Mediated Currents and Plasticity of Cerebellar Synapses in Mice Expressing the GluN1(F639A) Subunit. Alcohol Clin Exp Res 42:698-705
Cannady, Reginald; Rinker, Jennifer A; Nimitvilai, Sudarat et al. (2018) Chronic Alcohol, Intrinsic Excitability, and Potassium Channels: Neuroadaptations and Drinking Behavior. Handb Exp Pharmacol 248:311
Harlan, Benjamin A; Becker, Howard C; Woodward, John J et al. (2018) Opposing actions of CRF-R1 and CB1 receptors on VTA-GABAergic plasticity following chronic exposure to ethanol. Neuropsychopharmacology 43:2064-2074
Hanlon, Colleen A; Dowdle, Logan T; Henderson, J Scott (2018) Modulating Neural Circuits with Transcranial Magnetic Stimulation: Implications for Addiction Treatment Development. Pharmacol Rev 70:661-683
Hanlon, Colleen A; Dowdle, Logan T; Gibson, Nicole B et al. (2018) Cortical substrates of cue-reactivity in multiple substance dependent populations: transdiagnostic relevance of the medial prefrontal cortex. Transl Psychiatry 8:186
Gioia, Dominic A; Xu, Minfu; Wayman, Wesley N et al. (2018) Effects of drugs of abuse on channelrhodopsin-2 function. Neuropharmacology 135:316-327
Anton, Raymond F; Latham, Patricia K; Voronin, Konstantin E et al. (2018) Nicotine-Use/Smoking Is Associated with the Efficacy of Naltrexone in the Treatment of Alcohol Dependence. Alcohol Clin Exp Res 42:751-760

Showing the most recent 10 out of 209 publications