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 micro l saline], during conditioning phase, induced CPP in a dose-dependent manner. Additionally, intra-VTA administration of AM251 [5, 25 and 125 nmol/0.3 micro l 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

Capsazepine, a transient receptor potential vanilloid type 1 [TRPV1] antagonist, attenuates antinociceptive effect of CB1 receptor agonist, WIN55,212-2, in the rat nucleus cuneiformis

Introduction: Nucleus cuneiformis [NCF], as part of descending pain inhibitory system, cooperates with periaqueductal gray [PAG] and rostral ventromedial medulla [RVM] in supraspinal modulation of pain. Cannabinoids have analgesic effects in the PAG, RVM and NCF. The transient receptor potential vanilloid type 1[TRPV1] can be activated by anandamide and WIN55, 212-2 as a cannabinoid receptor agonist. The aim of the current study is to investigate the possible interplay between the cannabinoid and vanilloid systems for modulation of pain at the NCF. Methods: In this study, a cannabinoid receptor agonist, WIN55, 212-2 [15 µg/0.3 µl DMSO], and selective TRPV1 receptor antagonist, capsazepine [10, 25, 50 and100 nmol/0.3 µl DMSO], were microinjected bilaterally into the NCF, and tailflick and formalin tests were used to assess the animal's pain-related behaviors at 5-min intervals for a 60-min period. Results: Our findings demonstrated that analgesic effect of WIN55, 212-2 were dose-dependently attenuated by capsazepine in both tests. In the tail-flick test, capsazepine at both doses of 50 [P<0.01] and 100 [P<0.001] nmol could significantly prevent the antinociceptive effect of WIN55, 212-2 while capsazepine, in formalin test, could decreased its antinociceptive effect at the dose of 50 nmol [P<0.05] as well. On the other hand, solely administration of the highest dose of capsazepine in both tests did not alter the pain-related behaviors. Discussion: It suggests a possible role for TRPV1 receptors in NCF-mediated cannabinoid-induced antinociception