Chemical stimulation of the lateral hypothalamus induced seeking behaviors in rats: Involvement of orexin receptors in the ventral tegmental area

Orexinergic projections originated from the lateral hypothalamus (LH) to the ventral tegmental area (VTA) play essential role in reward-related behaviors. Our previous studies show that intra-LH injection of carbachol, as a cholinergic agonist, induces conditioned place preference (CPP) in rats. This study aimed to determine whether chemical stimulation of the LH alone can induce reinstatement or not, and whether intra-VTA orexin receptors are involved in the reinstatement of intra-LH carbachol-induced CPP in the rats. The animals were unilaterally treated by carbachol (250 nM) in the LH during 3-day conditioning phase. Then, they underwent an extinction phase without receiving carbachol, and on the reinstatement day, animals received a different priming dose of carbachol in the separate groups. Extinguished animals unilaterally received intra-VTA administration of SB334867 or TCS OX2 29 as orexin-1 or orexin-2 receptor antagonists to evaluate the role of orexin receptors before effective priming dose of carbachol on the reinstatement day. Findings showed that intra-LH microinjection of a priming dose of carbachol (25 and 50 nM) induced the reinstatement of LH chemical stimulation-induced CPP. Moreover, it was indicated that, intra-VTA administration of either SB334867 or TCS OX2 29 (10 and 30 nM) before to intra-LH injection of the priming dose of carbachol (50 nM) dose-dependently inhibited the reinstatement of intra-LH carbachol-induced CPP. Also, the orexin-2 receptor antagonist was a little more effective than orexin-1 receptor antagonist for inhibiting the reinstatement of LH chemical stimulation-induced CPP. The consequences propose that both orexin receptors in the VTA play roles in the reinstatement of intra-LH carbachol-induced CPP.