Indeed, PPAR-α agonists were also effective at the terminal regions in the nucleus accumbens, an area believed to be critical to abuse potential (84), especially the shell subregion (11, 12). That is, PPAR-α agonists blocked nicotine’s ability to induce excitation of dopamine neurons in the VTA, at doses that did not alter spontaneous firing rates; this effect was reversed by the PPAR-α antagonist MK886 (67, 68). PPAR-α agonists also attenuated nicotine-induced increases in dopamine levels in the nucleus accumbens shell at doses that had no effect on DA on their own; these effects were also reversed by MY886 at doses that were ineffective on its own (67, 68). Further, MK886, a PPAR-α antagonist, blocked URB597’s effects on nicotine-induced inhibition of medium spiny neuron activation induced by stimulation of the baso-lateral amygdala, an effect that was also found with cocaine- induced inhibition of medium spiny neuron activation induced by stimulation of the baso-lateral amygdala.
