Abstract
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.