The effects of PPAR-α agonists have been tested in both the cue-induced reinstatement and drug-induced reinstatement paradigms. That is, after acquisition of self-administration responding for nicotine under either a FR-1 or FR-5 schedule of reinforcement followed by extinction of the responding, responding was reinstated by priming injections of nicotine (25). In our studies (67, 68), pretreatment with the PPAR-α agonists WY14643 and clofibrate prior to nicotine-induced reinstatement attenuated reinstatement in rats and monkeys, as illustrated in monkeys in Figure 3; administration of the PPAR-α antagonist MK886 reversed the effects of WY14643 on nicotine-induced reinstatement (67). MK886 also reversed the effects of clofibrate on nicotine-induced reinstatement (67). However, unlike drug intake, where the effects of PPAR-α agonists seemed to be selective for nicotine, and perhaps alcohol, both nicotine-induced and cue-induced reinstatement to nicotine-seeking behavior in monkeys were blocked by clofibrate, and both of these effects were reversed by MK886 (67).
