Rewarding effect of ethanol-induced conditioned place preference in mice: Effect of the monoterpenoid linalool

Alcohol addiction is a chronic relapsing disease that is progressive and has severe detrimental health outcomes. The use of natural products has become popular for the treatment of side effects of drugs and substance abuse. Linalool is a monoterpenoid that exhibits several effects on the central nervous system. Linalool was identified to have beneficial effects on different mechanisms that are relevant in drug addiction or substance use disorder. The primary aim of the present study was to evaluate the therapeutic effect of linalool on the rewarding properties of alcohol in mice. Conditioned place preference (CPP) was established by intraperitoneal (i.p.) injection of ethanol (2 g/kg) during an 8-day conditioning trial. The effects of acamprosate and linalool on the rewarding properties of ethanol were tested in mice who received linalool (12.5, 25, and 50 mg/kg, i.p.) and acamprosate (300 mg/kg, i.p.) 30 min before each ethanol injection. CPP was extinguished by repeated testing, throughout which conditioned mice were administered daily linalool. Mice were lastly examined for reinstatement provoked by i.p. administration of single low-dose ethanol (0.4 g/kg, i.p.). Treatment with linalool reduced the acquisition and reinstatement, and precipitated the extinction of ethanol-induced CPP in mice. Acquisition and reinstatement of alcohol-induced CPP were significantly reduced by acamprosate, which also precipitated extinction. Ethanol alone and the combination with linalool or acamprosate did not alter locomotor activity. The results of this study suggest that linalool may have pharmacological effects for the treatment of alcohol addiction. In addition, further investigation is required to fully explore the benefits and possible adverse effects of linalool on alcohol addiction.