Buzzi, BelleKoseli, EdaAlkhlaif, YasminParker, AbigailMustafa, Mohammed A.Lichtman, Aron H.Buczynski, Matthew W.Damaj, M. Imad2025-02-182025-02-182023-07-110006-8993S0006-8993(23)00254-8 (PII)https://hdl.handle.net/10919/124611Nicotine and tobacco-related deaths remains a leading cause of preventable death and disease in the United States. Several studies indicate that modulation of the endocannabinoid system, primarily of the endocannabinoid 2-Arachidonoylglycerol (2-AG), alters nicotinic dependence behaviors in rodents. This study, using transgenic knock-out (KO) mice, evaluated the role of the two 2-AG biosynthesis enzymes, (Diacylglycerol lipase-α) DAGL-α and DAGL-β in spontaneous nicotine withdrawal. DAGL-α deletion prevents somatic and affective signs of nicotine withdrawal, while DAGL-β deletion plays a role in hyperalgesia due to nicotine withdrawal. These results suggest a differential role of these enzymes in the various signs of nicotine withdrawal. Our behavioral findings relate to the distribution of these enzymes with DAGL-β being highly expressed in macrophages and DAGL-α in neurons. This study offers new potential targets for smoking cessation therapies.5 page(s)application/pdfenIn CopyrightDiacylglycerol lipaseNicotine withdrawalMiceEndocannabinoidsAnimalsMice, KnockoutMiceSubstance Withdrawal SyndromeTobacco Use DisorderNicotineLipoprotein LipaseEndocannabinoidsArticle - Refereedhttps://doi.org/10.1016/j.brainres.2023.1484831817Buczynski, Matthew [0000-0001-5931-7107]374422501872-6240