In conclusion, our findings demonstrate that nicotine's ability to have rewarding effects and reinstate drug-seeking behavior after a period of abstinence are suppressed by PPAR-α activation, accomplished directly by PPAR-α agonists or indirectly by FAAH inhibition. These behavioral effects appear to be due to modulation of nicotine's excitatory effects on reward-related mesolimbic dopamine transmission. Notably, PPAR-α agonists and FAAH inhibitors appear to suppress nicotine reward and reinstatement much like the cannabinoid inverse agonist/antagonist rimonabant, but do not share the adverse psychoactive effects produced by medications that target cannabinoid CB1 receptors (3,9,19). Thus, PPAR-α is a promising new molecular target for the treatment of the devastating problem of tobacco dependence.
