Involvement of orexin-2 receptors in the CA1 region of the hippocampus in the extinction and reinstatement of methamphetamine-induced conditioned place preference in the rats

Abstract

The present study, regarding the orexin receptors having a pivotal role in reward-related psychostimulant use disorder (PUD), aimed to investigate the role of orexin-2 (OX2) receptors in the CA1 region of the hippocampus (HPC) in the extinction and reinstatement of methamphetamine (METH)-induced conditioned place preference (CPP). In the first set of investigations, to determine the role of OX2 receptors in the extinction of METH-induced CPP, rats were daily given (during the extinction) bilaterally intra-CA1 region different doses of TCS OX2 29 (1, 3, 10, and 30 nmol/0.5 μl 12% DMSO) as the selective OX2 receptor antagonist. Then, to demonstrate the role of OX2 receptors in the reinstatement of METH-induced CPP after the extinction was established, each rat bilaterally received TCS OX2 29 at the same doses in the CA1 region before injection of the sub-threshold (priming) dose of METH (0.25 mg/kg, sc) on the reinstatement day. The data revealed that the administration of TCS OX2 29 in the CA1 region reduces the mean extinction latency and suppresses the reinstatement of METH-seeking behavior in extinguished rats. Additionally, the potency of TCS OX2 29 to inhibit the reinstatement phase was higher compared to the potency of this drug to modulate the extinction phase of METH-induced CPP. Accordingly, it could be concluded that the blockade of the OX2 receptors in this area might be an essential application and potential therapeutics in treating METH use disorder.