Functional interaction between the orexin-1 and CB1 receptors within the nucleus accumbens in the conditioned place preference induced by the lateral hypothalamus stimulation

• Blockade of OX1 receptor in the NAc dose-dependently decreased the acquisition of LH-induced CPP.
• Blockade of OX1 receptors in the NAc decreased the expression of LH-induced CPP.
• Intra-accumbal OX1 receptor has a more important role in acquisition as compared to expression of the LH-induced CPP.
• There is a functional interaction between intra-accumbal OX1 and CB1 receptors in LH-induced CPP.

Several studies have shown that chemical stimulation of the lateral hypothalamus (LH) by carbachol induces the conditioned place preference (CPP) in rats. LH is the main source of the orexinergic neurons and sends projections to some areas of the brain such as the nucleus accumbens (NAc). We tried to determine the role of intra-accumbal orexin-1 (OX1) receptors in development (acquisition) and expression of reward-related behaviors induced by LH stimulation and involvement of CB1 cannabinoid receptors in this area. Adult male Wistar rats were unilaterally implanted by two separate cannulae into the LH and NAc. The CPP paradigm was done; conditioning scores and locomotor activities were recorded. The results showed that intra-accumbal administration of SB334867 as a selective OX1 receptor antagonist (1, 3, 10 and 30 nM/0.5 μl DMSO) 5 min before intra-LH carbachol (250 nM/0.5 μl saline) during 3-day conditioning phase, could dose-dependently inhibit the development of LH-induced CPP. In expression experiments, intra-NAc administration of SB334867 on the test day could decrease the expression of LH stimulation-induced CPP. Furthermore, concurrent intra-accumbal administration of effective/ineffective doses of SB334867 and AM251 (45 and 15 μM) as a CB1 receptor antagonist, before carbachol during the conditioning phase, could attenuate the development of LH stimulation-induced CPP. It seems that the orexinergic projection from the LH to the NAc is involved in the LH stimulation-induced CPP and OX1 receptor in the NAc has a substantial role in this phenomenon. Our findings also suggest the existence a functional interaction between OX1 and CB1 receptors within the NAc in place preference.