title: Activation of PPARγ by pioglitazone potentiates the effects of naltrexone on alcohol drinking and relapse in msP rats.
abstract: 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.affiliation: School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Stopponi
authors.forename: Giordano
authors.initials: G
authors.lastname: de Guglielmo
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Somaini
authors.forename: Andrea
authors.initials: A
authors.lastname: Cippitelli
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Cannella
authors.forename: Marsida
authors.initials: M
authors.lastname: Kallupi
authors.forename: Massimo
authors.initials: M
authors.lastname: Ubaldi
authors.forename: Markus
authors.initials: M
authors.lastname: Heilig
authors.forename: Gregory
authors.initials: G
authors.lastname: Demopulos
authors.forename: George
authors.initials: G
authors.lastname: Gaitanaris
authors.forename: Roberto
authors.initials: R
authors.lastname: Ciccocioppo
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy*; D000818:Animals; D003463:Cues; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009271:Naltrexone / Q000494:pharmacology / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D047495:PPAR gamma / Q000378:metabolism*; D000077205:Pioglitazone; D051381:Rats; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D015016:Yohimbine
chemical_list: D007004:Hypoglycemic Agents; D009292:Narcotic Antagonists; D047495:PPAR gamma; D045162:Thiazolidinediones; D015016:Yohimbine; D009271:Naltrexone; D000077205:Pioglitazone
keywords: Abuse; Addiction; Drug Seeking; Ethanol; Self-Administration