results not only suggest a selective effect of PPAR-γ agonists on intake of alcohol, as opposed to natural reinforcers, they also suggest that decreases in alcohol self-administration were not due to a non-specific inhibition of behavior or a decrease in the ability to perform a response. Importantly, in this study, it was also demonstrated that PPAR-γ agonists, while reducing alcohol drinking, did not modify blood glucose levels nor did they affect alcohol metabolism, ruling out the possibility that metabolic effects might have contributed to drug effects. Rather, PPAR-γ agonists appear to have affected the motivation to take alcohol. In a subsequent study it was also shown that combining pioglitazone with naltrexone, a drug currently used for alcohol addiction treatment in humans, leads to a more pronounced inhibition of drinking compared to the two drugs given alone (74). More recently, experiments were conducted to evaluate the effect of PPARγ agonists on opiate intake. Results revealed that treatment with pioglitazone significantly reduced intravenous self-administration of heroin under both fixed-ratio and progressive-ratio schedules of reinforcement. This effect was maintained over repeated days of treatment (75).
