Inhibition of monoacylglycerol lipase (MAGL) enhances cue-induced reinstatement of nicotine-seeking behavior in mice.
Tobacco smoking is still a major population health issue. The endocannabinoid system has been shown to control drug-seeking behaviors. There are two main endocannabinoids: anandamide degraded by fatty acid amide hydrolase (FAAH) and 2-arachidonoylglycerol (2-AG) degraded by monoacylglycerol lipase (MAGL).



The role of MAGL has only been explored recently, and so far, no study have been performed to evaluate the effects of MAGL inhibitor on nicotine reinforcing properties and cue-induced reinstatement of nicotine seeking.



Here, we investigated the effects of the MAGL inhibitor JZL184 on nicotine self-administration under fixed and progressive-ratio schedules of reinforcement and on cue-induced reinstatement of nicotine seeking in mice. We also evaluated the effects of JZL184 on food self-administration for possible non-specific effects.



JZL184 (0, 8, and 16 mg/kg) did not affect food taking, nicotine taking, or motivation for nicotine. MAGL inhibition by JZL184 (16 mg/kg) increased reinstatement of previously extinguished nicotine seeking induced by presentation of nicotine-associated cues, but did not produce reinstatement on its own.



This study implicates involvement of 2-AG in nicotine-seeking behaviors.
Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), 33 Russell Street, Toronto, ON, M5S 2S1, Canada.
Jose M
JM
Trigo
Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), 33 Russell Street, Toronto, ON, M5S 2S1, Canada. bernard.lefoll@camh.ca.|Addictions Division, CAMH, Toronto, ON, Canada. bernard.lefoll@camh.ca.|Alcohol Research and Treatment Clinic, Addiction Medicine Services, Ambulatory Care and Structured Treatments, Centre for Addiction and Mental Health, Toronto, ON, Canada. bernard.lefoll@camh.ca.|Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada. bernard.lefoll@camh.ca.|Department of Pharmacology, University of Toronto, Toronto, ON, Canada. bernard.lefoll@camh.ca.|Department of Psychiatry, Division of Brain and Therapeutics, University of Toronto, Toronto, ON, Canada. bernard.lefoll@camh.ca.|Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada. bernard.lefoll@camh.ca.
Bernard
B
Le Foll
D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology*; D003463:Cues; D058999:Drug-Seeking Behavior / Q000187:drug effects* / Q000502:physiology; D005989:Glycerides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors*; D009538:Nicotine / Q000008:administration & dosage*; D010880:Piperidines / Q000494:pharmacology*; D012054:Reinforcement, Psychology; D012646:Self Administration
D052117:Benzodioxoles; D005989:Glycerides; C534333:JZL 184; D010880:Piperidines; D009538:Nicotine; D008994:Monoacylglycerol Lipases
2-arachidonoylglycerol; Mice; Nicotine; Reinstatement; Self-administration