administration of the cannabinoid methanandamide (a hydrolysis-resistant analog of anandamide), but rather by i.c.v. administration of the non-cannabinoid FAAH substrate, OEA (8). In addition, in vitro activation of VTA dopamine neurons by nicotine in brain slices was prevented by both OEA and PEA, but not by methanandamide (8). OEA and PEA, are potent agonists of PPAR-α, which is expressed in many areas of the rat brain [including cortex, VTA, midbrain, medulla, hippocampus, substantia nigra and olfactory tubercle (10-14)] and might regulate cholinergic neurotransmission and learning and memory processes (15,16). These findings suggest that FAAH inhibition counteracts the rewarding effects of nicotine by activating PPAR-α.
