We recently reported that a FAAH-inhibiting drug can counteract addiction-related effects of nicotine in several animal models (7-9). In rats, FAAH inhibition suppressed the development of nicotine-induced conditioned place-preference and nicotine self-administration, widely-used animal models of nicotine's habit-forming effects (9). FAAH inhibition also suppressed reinstatement of nicotine-seeking, an animal model of relapse (7). In addition to these behavioral effects, we found that FAAH inhibition prevented the neurochemical and electrophysiological effects of nicotine on reward circuits of the brain that underlie addictive behavior. That is, FAAH inhibition prevented nicotine-induced elevations of the neurotransmitter dopamine in the nucleus accumbens shell (9), and it attenuated nicotine-induced excitation of dopamine neurons in the ventral tegmental area (VTA) (8). Surprisingly, the latter effect did not appear to be mediated by cannabinoid receptors since it was not mimicked in vivo by intravenous (i.v.) or intracerebroventricular (i.c.v.) 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
