In the present study, we combined behavioral, neurochemical and electrophysiological approaches to determine whether directly-acting PPAR-α agonists can counteract several reward- and dependence-related effects of nicotine: (1) nicotine self-administration in rats and squirrel monkeys; (2) reinstatement of nicotine-seeking precipitated by re-exposure to nicotine in rats and squirrel monkeys after a period of abstinence; (3) the interoceptive effects of nicotine in a drug-discrimination procedure in rats; (4) electrophysiological effects of nicotine on the activity of VTA dopamine neurons in anesthetized rats; and (5) nicotine-induced elevations in dopamine levels in the nucleus accumbens shell of freely-moving rats.
