Linalool Attenuates Acquisition and Reinstatement and Accelerates the Extinction of Nicotine-Induced Conditioned Place Preference in Male Mice

Abstract

Background: Nicotine is the addictive agent in tobacco products. The monoterpene linalool is the main ingredient in the essential oils of various aromatic plants. It has previously been demonstrated that linalool has beneficial effects on some mechanisms that are important in drug addiction. Objectives: The goal of the current study was to investigate the effect of linalool on nicotine-induced conditioned place preference (CPP) in male mice. Methods: CPP was induced by administering intraperitoneal (i.p.) injection of nicotine (0.5 mg/kg) during the conditioning phase. The effects of nicotinic acetylcholine receptor partial agonist varenicline and linalool on the rewarding characteristics of nicotine were tested in mice with administration of linalool (12.5, 25, and 50 mg/kg, i.p.), varenicline (2 mg/kg, i.p.) or saline 30 minutes before nicotine injection. CPP was extinguished by repeated testing, during which conditioned mice were administered varenicline and linalool every day. One day after the last extinction trial, mice that received linalool, varenicline or saline 30 minutes before a priming injection of nicotine (0.1 mg/kg, i.p.) were immediately tested for reinstatement of CPP. Results: Linalool attenuated nicotine acquisition (50 mg/kg, p < .01) and reinstatement (25 and 50 mg/kg, respectively p < .05, p < .01) and accelerated the extinction of nicotine-induced CPP (50 mg/kg, p < .05). Linalool exhibited similar effects on the reference drug varenicline in the CPP phases. Conclusion: These results suggest that linalool may be helpful as an adjuvant for the treatment of nicotine use disorder.