Activation of PPARγ by Pioglitazone Potentiates the Effects of Naltrexone on Alcohol Drinking and Relapse in msP Rats
Version of Record online: 29 MAR 2013
Copyright © 2013 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 37, Issue 8, pages 1351–1360, August 2013
How to Cite
Stopponi, S., de Guglielmo, G., Somaini, L., Cippitelli, A., Cannella, N., Kallupi, M., Ubaldi, M., Heilig, M., Demopulos, G., Gaitanaris, G. and Ciccocioppo, R. (2013), Activation of PPARγ by Pioglitazone Potentiates the Effects of Naltrexone on Alcohol Drinking and Relapse in msP Rats. Alcoholism: Clinical and Experimental Research, 37: 1351–1360. doi: 10.1111/acer.12091
- Issue online: 26 JUL 2013
- Version of Record online: 29 MAR 2013
- Manuscript Accepted: 8 JAN 2013
- Manuscript Received: 26 JUN 2012
- University of Camerino
- Drug Seeking;
Pioglitazone is a selective peroxisome proliferator-activated receptor γ (PPARγ) agonist used for the treatment of insulin resistance and type 2 diabetes. Previous studies conducted in our laboratory showed that activation of PPARγ by pioglitazone reduces alcohol drinking, stress-induced relapse, and alcohol withdrawal syndrome in rats. Pioglitazone was not able to prevent relapse elicited by alcohol cues. Conversely, the nonselective opioid antagonist naltrexone has been shown to reduce alcohol drinking and cue- but not stress-induced relapse in rodents.
Based on these findings, this study was sought to determine the efficacy of pioglitazone and naltrexone combination on alcohol intake and relapse behavior. Genetically selected alcohol-preferring Marchigian Sardinian (msP) rats were used for the study.
Pioglitazone (10 and 30 mg/kg) and naltrexone (0.25 and 1.0 mg/kg) each individually reduced alcohol drinking in msP rats. The combination of the 2 drugs resulted in a more potent alcohol drinking reduction than single agents. Confirming previous studies, pioglitazone (10 and 30 mg/kg) significantly reduced relapse induced by the pharmacological stressor yohimbine (1.25 mg/kg) but not by cues predictive of alcohol availability. Conversely, naltrexone reduced reinstatement of drug seeking elicited by alcohol cues but not by yohimbine.
The drug combination was effective in reducing both relapse behaviors. These findings open new vistas in the use pioglitazone in combination with naltrexone for the treatment of alcoholism.