Differential Roles of Intra-accumbal Orexin Receptors in Acquisition and Expression of Methamphetamine-Induced Conditioned Place Preference in the Rats.

A large amount of document has revealed that the orexin system in the reward circuity, including the nucleus accumbens (NAc), contributes to the modification of drug reinforcement. It has proven that the orexin receptors (OXRs) are expressed on dopamine terminals in the NAc; therefore, it can modulate reward-related behaviors. In the present study, the conditioned place preference (CPP) paradigm was used to evaluate the role of OXRs in the NAc in the acquisition and expression of methamphetamine (METH)-induced CPP. Based on previous studies, animals received METH (1 mg/kg; sc) on a 5-day schedule to induce CPP. The rats bilaterally received SB334867, OX1R antagonist, or TCS OX2 29, OX2R antagonist, (1, 10, and 30 nM/0.5 µl DMSO 12%) over five days of conditioning by METH to display the role of OXRs in reward acquisition. Moreover, the rats bilaterally received SB334867 or TCS OX2 29 in the NAc before the post-conditioning test to consider the impact of OXR antagonists on the expression of METH-induced CPP. The data revealed that the administration of SB334867 or TCS OX2 29 in the NAc led to a decrease in the acquisition of METH-induced CPP. Additionally, intra-accumbal injection of OX1R antagonist inhibited the expression of METH-induced CPP, while the OX2R antagonist failed to change this expression. Finally, the intra-NAc microinjection of both OXR antagonists was more effective in inhibiting acquisition than blocking the expression phase of METH. Data from the current study confirms that OXRs in the NAc regulate the reward-related effects of METH.