LY-2183240 enhances reward-seeking behavior with inducing neuronal excitation and early apoptosis in mouse
Yu Yeong Jeong,
Jae Hong Yoo,
Seo Yule Jeong,
Myunghoon Lee,
Su Jeong Park,
Na Young Lim,
Seung Won Son,
Kyung-Seok Han,
Dong Ho Woo
Affiliations
Yu Yeong Jeong
Center for Global Biopharmaceutical Research Korea Institute of Toxicology, KRICT, Daejeon 34114, South Korea; Department of Biological Sciences, Chungnam National University, Daejeon 34134, South Korea
Jae Hong Yoo
Department of Biological Sciences, Chungnam National University, Daejeon 34134, South Korea
Seo Yule Jeong
Center for Global Biopharmaceutical Research Korea Institute of Toxicology, KRICT, Daejeon 34114, South Korea
Myunghoon Lee
Department of Biological Sciences, Chungnam National University, Daejeon 34134, South Korea
Su Jeong Park
Pharmacology and Narcotics Research Division, National Institute of Food & Drug Safety Evaluation, Cheongju-si, South Korea
Na Young Lim
Pharmacology and Narcotics Research Division, National Institute of Food & Drug Safety Evaluation, Cheongju-si, South Korea
Seung Won Son
Pharmacology and Narcotics Research Division, National Institute of Food & Drug Safety Evaluation, Cheongju-si, South Korea
Kyung-Seok Han
Department of Biological Sciences, Chungnam National University, Daejeon 34134, South Korea; Corresponding author
Dong Ho Woo
Center for Global Biopharmaceutical Research Korea Institute of Toxicology, KRICT, Daejeon 34114, South Korea; Human and Environmental Toxicology, University of Science and Technology, Daejeon 34114, South Korea; Corresponding author
Summary: Cannabinoids interact with cannabinoid receptors, influencing diverse central nervous system (CNS) and peripheral functions, including anxiety, depression, and cognition. CB1 and CB2 receptors modulate signaling cascades via G-protein coupling, with anandamide acting as an endogenous ligand for CB1 receptors. LY-2183240, a putative endocannabinoid transport blocker, elevates brain anandamide levels, showing therapeutic potential in pain management and alcohol-related behaviors. LY-2183240 enhances neuronal excitability and is classified as a new psychoactive substance (NPS). However, its precise cellular mechanisms within the CNS remain poorly understood. In this study, the effect of LY-2183240 on cortical neurons and reward-seeking behavior is investigated. Our results indicate enhanced neuronal excitability and reward-seeking behavior induction by LY-2183240, shedding light on its pharmacological profile and NPS-associated risks. Our research underscores the importance of further understanding the cellular mechanisms of LY-2183240 to inform regulatory efforts and mitigate public health risks.
