LY-2183240 enhances reward-seeking behavior with inducing neuronal excitation and early apoptosis in mouse

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...

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Published iniScience Vol. 27; no. 11; p. 111069
Main Authors Jeong, Yu Yeong, Yoo, Jae Hong, Jeong, Seo Yule, Lee, Myunghoon, Park, Su Jeong, Lim, Na Young, Son, Seung Won, Han, Kyung-Seok, Woo, Dong Ho
Format Journal Article
LanguageEnglish
Published Elsevier Inc 01.11.2024
Elsevier
Subjects
Biological sciences
Natural sciences
Neuroscience
Pharmacology
Neuroscience
Pharmacology
Biological sciences
Natural sciences
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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. [Display omitted] •LY-2183240, a new psychoactive substance, induces neuronal excitability in vitro and ex vivo•LY-2183240 causes glutamate excitotoxicity and induces early apoptosis•LY-2183240 acts as a reinforcer, which may indicate some potential for abuse Pharmacology; Natural sciences; Biological sciences; Neuroscience
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2024.111069