Administration of Cannabinoid Receptor Antagonist into the Ventral Tegmental Area Could Inhibit Conditioned Place Preference Induced by Chemical Stimulation of the Lateral Hypothalamus

Orexinergic projection originated from the lateral hypothalamus (LH) to the ventral tegmental area (VTA) has an important role in the acquisition of drug conditioned place preference (CPP). In the present study, we tried to evaluate the effect of LH stimulation on conditioned place preference paradigm and role of CB1 receptors located in the VTA in development of reward-related behaviors in rats. One hundred twenty adult male Wistar rats weighing 220-330 g were unilaterally implanted by two separate cannulae into the LH and VTA. The CPP paradigm was done. Our findings showed that unilateral intra-LH administration of carbachol (62.5, 125 and 250 nmol/0.5 µl saline), during conditioning phase, induced CPP in a dose-dependent manner. Additionally, intra-VTA administration of AM251 (5, 25 and 125 nmol/0.3 µl DMSO) as a CB1 receptor antagonist, just 5 min before carbachol during the 3-day conditioning phase, could dose dependently inhibit the development of LH stimulation-induced CPP in the rats. It is supposed that the projection from LH to VTA is involved in LH chemical stimulation-induced CPP and CB1 receptor in the VTA has a modulatory role in this phenomenon.