Therapeutic Potential of Methanolic Extract of Areca catechu Nut in Treating Nicotine Use Disorder: evidence from preclinical mouse behavioral models.

Objectives: Arecoline, the main bioactive compound in Areca catechu nut, interacts with nicotinic acetylcholine receptors (α4β2 and α7), suggesting potential in reducing nicotine cravings and withdrawal symptoms. This study evaluates the therapeutic potential of methanolic Areca catechu nut extract (MAN) against nicotine dependence and withdrawal in C57BL/6J mice. Methods: A modified runway model assessed nicotine-seeking behavior. Antidopaminergic effects and locomotor activity were measured via the haloperidol-induced catalepsy model and actophotometer. Behavioral models were used to evaluate MAN's effects on nicotine withdrawal symptoms anxiety (elevated plus maze, open field, marble burying), depression (forced swim, tail suspension), social interaction, anhedonia (sucrose preference), memory (elevated plus maze), and hyperalgesia (hot plate assay). Results: MAN (25 and 50 mg/kg, p.o.) showed antidopaminergic activity, reduced nicotine craving, and alleviated withdrawal symptoms (anxiety, depression, anhedonia, memory impairment, hyperalgesia) by enhancing serotonergic neurotransmission. Conclusion: MAN shows potential as a therapeutic candidate for nicotine use disorder.