The role of fatty acid amide hydrolase inhibition in nicotine reward and dependence.
The endogenous cannabinoid anandamide (AEA) exerts the majority of its effects at CB1 and CB2 receptors and is degraded by fatty acid amide hydrolase (FAAH). FAAH KO mice and animals treated with FAAH inhibitors are impaired in their ability to hydrolyze AEA and other non-cannabinoid lipid signaling molecules, such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). AEA and these other substrates activate non-cannabinoid receptor systems, including TRPV1 and PPAR-α receptors. In this mini review, we describe the functional consequences of FAAH inhibition on nicotine reward and dependence as well as the underlying endocannabinoid and non-cannabinoid receptor systems mediating these effects. Interestingly, FAAH inhibition seems to mediate nicotine dependence differently in mice and rats. Indeed, pharmacological and genetic FAAH disruption in mice enhances nicotine reward and withdrawal. However, in rats, pharmacological blockade of FAAH significantly inhibits nicotine reward and has no effect in nicotine withdrawal. Studies suggest that non-cannabinoid mechanisms may play a role in these species differences.
Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, 1217 E Marshall St, Richmond, VA 23298, USA. pipatel@vcu.edu
Pretal P
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Muldoon
Aron H
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Lichtman
Loren H
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Parsons
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Damaj
D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000818:Animals; D063388:Endocannabinoids / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D012201:Reward; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000503:physiopathology; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000523:psychology; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D009538:Nicotine; D018722:Nicotinic Agonists; D000099252:Fatty Acid Amide Hydrolases