Differential roles of diacylglycerol lipase (DAGL) enzymes in nicotine withdrawal

Brain Res. 2023 Oct 15:1817:148483. doi: 10.1016/j.brainres.2023.148483. Epub 2023 Jul 11.


Nicotine 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.

Keywords: Diacylglycerol lipase; Endocannabinoids; Mice; Nicotine withdrawal.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Endocannabinoids
  • Lipoprotein Lipase
  • Mice
  • Mice, Knockout
  • Nicotine
  • Substance Withdrawal Syndrome*
  • Tobacco Use Disorder*


  • Nicotine
  • Lipoprotein Lipase
  • Endocannabinoids