Premium
Activation of PPAR γ by Pioglitazone Potentiates the Effects of Naltrexone on Alcohol Drinking and Relapse in ms P Rats
Author(s) -
Stopponi Serena,
Guglielmo Giordano,
Somaini Lorenzo,
Cippitelli Andrea,
Cannella Nazzareno,
Kallupi Marsida,
Ubaldi Massimo,
Heilig Markus,
Demopulos Gregory,
Gaitanaris George,
Ciccocioppo Roberto
Publication year - 2013
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12091
Subject(s) - pioglitazone , naltrexone , yohimbine , pharmacology , alcohol , agonist , endocrinology , medicine , alcohol dependence , insulin resistance , opioid , antagonist , type 2 diabetes , diabetes mellitus , receptor , chemistry , biochemistry
Background Pioglitazone is a selective peroxisome proliferator‐activated receptor γ ( PPAR γ) agonist used for the treatment of insulin resistance and type 2 diabetes. Previous studies conducted in our laboratory showed that activation of PPAR γ 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. Methods 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 M archigian S ardinian (ms P ) rats were used for the study. Results Pioglitazone (10 and 30 mg/kg) and naltrexone (0.25 and 1.0 mg/kg) each individually reduced alcohol drinking in ms P 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. Conclusions 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.