Effects of concurrent blockade of OX2 and CB1 receptors in the ventral tegmental area on nicotine-induced place preference in rats

Abstract

In this study, the role of orexin-2 (OX2) and cannabinoid-1 (CB1) receptors and their potential interaction within the ventral tegmental area (VTA) on nicotine-induced place preference, was examined in male rats. A 5-day conditioned place preference (CPP) paradigm was used. Nicotine (0.5 mg/kg; s.c.) induced a significant CPP, without any effect on the locomotor activity during the testing phase. TCS-OX2-29 (0.4, 0.8 and 4 μg/rat), as a selective OX2 receptor antagonist and AM251 (0.2, 1 and 2 μg/rat), as a selective cannabinoid CB1 receptor antagonist, individually or simultaneously were microinjected bilaterally into the VTA. The results showed that administration of AM251 (1 and 2 μg/rat) or TCS-OX2-29 (0.4, 0.8 and 4 μg/rat) into the VTA, during the 3-day conditioning phase or testing day, could dose-dependently inhibit the development of nicotine-induced CPP, in the acquisition or expression, respectively. Concurrent administration of ineffective doses of TCS-OX2-29 and AM251 into the VTA could not affect conditioning scores. The findings of this study support the possible role of OX2 and CB1 receptors in the VTA, in the acquisition and the expression of nicotine-induced place preference. Furthermore, our data suggest that there is a possible interaction between the VTA orexinergic and cannabinoid systems in nicotine-induced place preference.