BACKGROUND: 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. 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 Marchigian Sardinian (msP) 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 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. 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.
BACKGROUND: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. 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 Marchigian Sardinian (msP) 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 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. 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.
Authors: Joy M Schmitz; Charles E Green; Khader M Hasan; Jessica Vincent; Robert Suchting; Michael F Weaver; F Gerard Moeller; Ponnada A Narayana; Kathryn A Cunningham; Kelly T Dineley; Scott D Lane Journal: Addiction Date: 2017-07-03 Impact factor: 6.526
Authors: Milky Kohno; Jeanne Link; Laura E Dennis; Holly McCready; Marilyn Huckans; William F Hoffman; Jennifer M Loftis Journal: Pharmacol Biochem Behav Date: 2019-01-26 Impact factor: 3.533
Authors: Giordano de Guglielmo; Miriam Melis; Maria Antonietta De Luca; Marsida Kallupi; Hong Wu Li; Kevin Niswender; Antonio Giordano; Martina Senzacqua; Lorenzo Somaini; Andrea Cippitelli; George Gaitanaris; Gregory Demopulos; Ruslan Damadzic; Jenica Tapocik; Markus Heilig; Roberto Ciccocioppo Journal: Neuropsychopharmacology Date: 2014-09-14 Impact factor: 7.853
Authors: Jennifer R Schroeder; Karran A Phillips; David H Epstein; Michelle L Jobes; Melody A Furnari; Ashley P Kennedy; Markus Heilig; Kenzie L Preston Journal: Psychopharmacology (Berl) Date: 2018-08-06 Impact factor: 4.530