title: The selective anandamide transport inhibitor VDM11 attenuates reinstatement of nicotine seeking behaviour, but does not affect nicotine intake.
abstract: OBJECTIVE
  The endocannabinoid system appears to play a pivotal role in mediating the rewarding and reinforcing effects of nicotine. Recent studies have shown that the inhibition of fatty acid amide hydrolase (FAAH) attenuates reinstatement of nicotine-seeking induced by nicotine priming and nicotine-associated cues. FAAH hydrolyses the endogenous endocannabinoid anandamide, as well as other non-cannabinoid ligands such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). As OEA and PEA can attenuate both nicotine-taking and nicotine-seeking behaviour, the specific role of anandamide remains unclear. In this study, we have tested the selective anadamide uptake inhibitor, VDM11, which elevates anandamide levels without affecting levels of OEA/PEA, on nicotine-taking and nicotine-seeking behaviour.
  
  
  METHODS
  We used a nicotine intravenous self-administration model in rats to assess the effect of VDM11, given i.p., on nicotine taking using fixed and progressive ratio schedules of reinforcement as well as on reinstatement of nicotine-seeking induced by nicotine priming and nicotine-associated cues.
  
  
  RESULTS
  VDM11 did not affect levels of responding for nicotine under fixed-ratio and progressive-ratio schedules of reinforcement. In contrast, VDM11 dose-dependently attenuated reinstatement of nicotine-seeking behaviour induced by nicotine-associated cues and nicotine priming.
  
  
  CONCLUSIONS
  These results indicate that ligands elevating anandamide levels could have therapeutic value for preventing relapse into nicotine-seeking behaviour and should be tested in humans trying to quit smoking.
authors.affiliation: Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, Toronto, Canada.
authors.forename: Islam
authors.initials: I
authors.lastname: Gamaleddin
authors.forename: Mihail
authors.initials: M
authors.lastname: Guranda
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldberg
authors.forename: Bernard
authors.initials: B
authors.lastname: Le Foll
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003216:Conditioning, Operant; D058999:Drug-Seeking Behavior; D063388:Endocannabinoids; D005108:Extinction, Psychological; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D053284:Polyunsaturated Alkamides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012055:Reinforcement Schedule; D012646:Self Administration; D014029:Tobacco Use Disorder
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; C462953:N-(2-methyl-3-hydroxyphenyl)-5,8,11,14-eicosatetraenamide; D053284:Polyunsaturated Alkamides; D009538:Nicotine; C078814:anandamide