Evaluation of the Effect of Caffeine on the Acquisition and Expression of Nicotine-Induced Conditioned Place Preference

Abstract

Background: Addiction is a chronic condition characterized by persistent, uncontrolled drug seeking and use despite harmful consequences. Nicotine and caffeine are among the most widely used psychoactive substances worldwide, largely due to the high prevalence of tobacco smoking and coffee consumption. Moreover, use of these two substances commonly overlaps within the same individuals. Objectives: This study examined whether caffeine modulates the acquisition and expression of nicotine-induced conditioned place preference (CPP) in male mice. Methods: The CPP apparatus consisted of two spacious conditioning chambers. For each mouse, the time spent in the chamber associated with drug exposure was measured during the preconditioning and postconditioning sessions. The CPP score was calculated by subtracting the time spent in the drug-associated chamber before conditioning from the corresponding time recorded after conditioning. Male mice were randomly assigned to eight groups (n = 6 per group), and the study was conducted in two phases: acquisition and expression. During the CPP acquisition phase, mice received subcutaneous injections of caffeine at three doses (5, 10, or 20 mg/kg) concurrently with nicotine (0.5 mg/kg) during conditioning. During the CPP expression phase, nicotine was administered during conditioning, whereas caffeine was administered on the test day. Results: A significant difference was observed between the saline and nicotine groups, indicating that nicotine induced a significant CPP (P < 0.05). During the acquisition phase, coadministration of caffeine (5 mg/kg, s.c.) prevented the development of nicotine-induced CPP. Furthermore, during the expression phase, caffeine administration reduced the expression of nicotine-induced CPP. Conclusions: Although the present study did not demonstrate a synergistic interaction between caffeine and nicotine, the findings indicate that caffeine can attenuate the rewarding effects of nicotine in the CPP model.