Research ReportInvolvement of orexin-1 and orexin-2 receptors within the dentate gyrus of the hippocampus in the acquisition, expression and extinction of lateral hypothalamic-induced conditioned place preference in the rats

- Orexin receptors in the dentate gyrus involve in the acquisition, expression of the LH-induced CPP.
- Blockade of intra-DG OX1 and OX2 receptors dose-dependently attenuated acquisition of LH-induced CPP.
- OX1 receptor in the DG has more important role on the development of LH-induced CPP.
- Intra-DG administration of OX1 and OX2 receptor antagonists attenuated expression of LH-induced CPP.
- Blockade of OX1 but not OX2 receptors in the DG shortened the extinction of LH-induced CPP.

Orexinergic projections originating from the lateral hypothalamus (LH) have an important role in the acquisition of the LH-stimulation conditioned place preference (CPP). Among the brain areas associated with reward processing, LH orexinergic neurons send projections to the dentate gyrus (DG) region of the hippocampus, and it has been shown that orexin receptors are expressed in the DG. In this study, we investigated the role of intra-DG orexin-1 (OX1) and orexin-2 (OX2) receptors on acquisition, expression and extinction of CPP induced by stimulation of the LH. Rats were unilaterally implanted by two separate cannulae into the LH and DG. The CPP paradigm was done; conditioning scores and locomotor activities were recorded by Ethovision software. The results showed that intra-DG administration of SB334867, a selective OX1r antagonist, and TCS OX2 29, a selective OX2r antagonist, (0.5, 5, 12.5 and 50 nM/0.5 µl DMSO) before carbachol microinjection (250 nM; effective dose) during the 3-days conditioning phase, dose-dependently inhibited the development of LH stimulation-induced CPP in the rats. However, this reduction in OX1r antagonist treated groups was more than that in OX2r antagonist treated animals. In addition, these antagonists decreased the expression of LH-induced CPP. Moreover, OX1r but not OX2r antagonist could shorten the extinction duration of place preference. We conclude that the orexinergic projections from the LH to DG are involved in the development, expression and extinction of CPP induced by LH stimulation.