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

Belle Buzzi; Eda Koseli; Yasmin Alkhlaif; Abigail Parker; Mohammed A Mustafa; Aron H Lichtman; Matthew W Buczynski; M Imad Damaj

doi:10.1016/j.brainres.2023.148483

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.

Authors

Belle Buzzi¹, Eda Koseli¹, Yasmin Alkhlaif¹, Abigail Parker¹, Mohammed A Mustafa¹, Aron H Lichtman², Matthew W Buczynski³, M Imad Damaj⁴

Affiliations

¹ Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.
² Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA; Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, USA.
³ School of Neuroscience, Virginia Polytechnic and State University, Blacksburg, VA, USA.
⁴ Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA; Translational Research Initiative for Pain and Neuropathy, Virginia Commonwealth University, Richmond, VA, USA.

PMID: 37442250
PMCID: PMC10529956 (available on 2024-10-15)
DOI: 10.1016/j.brainres.2023.148483

Abstract

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*

Substances

Nicotine
Lipoprotein Lipase
Endocannabinoids

Abstract

Publication types

MeSH terms

Substances

Grants and funding