Chemical stimulation of the lateral hypothalamus induces conditioned place preference in rats: Involvement of OX1 and CB1 receptors in the ventral tegmental area

Orexinergic projection originated from the lateral hypothalamus (LH) to the ventral tegmental area (VTA) has an important role in the acquisition of morphine conditioned place preference (CPP). However, little if any is known about the function and/or effect of orexin on CPP in rats. In the present study, we investigated the direct effect of orexinergic neurons on acquisition of CPP by chemical stimulation of LH and involvement of orexin-A and CB1 receptors within the VTA in development of reward-related behaviors. 129 adult male albino Wistar rats weighing 220–320 g were unilaterally implanted by two separate cannulae into the LH and VTA. The CPP paradigm was done; conditioning score and locomotor activity were recorded by Ethovision software. The results showed that unilateral intra-LH administration of carbachol (62.5, 125 and 250 nmol/0.5 μl saline) as a cholinergic agonist, during conditioning phase, induced CPP in a dose-dependent manner. The maximal effect was shown at the dose of 250 nmol (P < 0.001) compared to vehicle (saline) group. However, intra-VTA administration of SB334867 as a selective orexin-A receptor antagonist (0.1, 1 and 10 nmol/0.3 μl DMSO) and 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 orexinergic projection from LH to VTA is involved in LH chemical stimulation-induced CPP and orexin-A receptor in the VTA has a substantial role in this phenomenon. Our findings also suggest the existence of cross-talk between cannabinoid and orexinergic systems within the VTA in conditioned place preference paradigm.

Research highlights▶ Chemical stimulation of the lateral hypothalamus (LH) produced conditioned place preference in the rats. ▶ Administration of OX1 receptor antagonist in the VTA inhibited the development of LH stimulation-induced conditioned place preference. ▶ It seems that stimulation of LH orexinergic neurons could directly induce the reward-related behaviors in part, via excitation of VTA neurons in the rats. ▶ Intra-VTA administration of CB1 receptor antagonist could inhibit conditioned place preference similar to OX1 receptor antagonist. ▶ It seems that OX1 receptor and CB1 receptor have a common pathway in reward-related behaviors processing in animal models.