Recent evidence suggests that drugs targeting PPARs might be effective in treating drug dependence (for review see 28). Retinoic acid is the only known RXR ligand and, interestingly, retinoic acid signaling was implicated in acute ethanol responses in mice 22. Also, pioglitazone and rosiglitazone (PPARγ agonists) reduced ethanol consumption in rats 58, 59. Intracerebroventricular administration of a PPARγ antagonist blocked the reduction in ethanol consumption, suggesting that this effect is mediated by central PPARγ receptors 59. Additionally, pioglitazone and rosiglitazone reduced ethanol withdrawal severity and stress-induced reinstatement of ethanol consumption in dependent rats without altering food or saccharine self-administration 59. Clofibrate, a PPARα agonist, prevented acquisition of nicotine dependence in naïve rats and monkeys and decreased nicotine self-administration in nicotine-dependent rats and monkeys 39. Thus, in addition to their known usefulness in cardiovascular disease and type II diabetes mellitus 49, PPAR agonists might be a potential treatment for alcohol dependence and other addictions.
