Blockade of orexin receptors in the hippocampal dentate gyrus reduced the extinction latency of morphine-induced place preference in male rats.

Relapse to drugs such as opioids is a major challenge in addiction therapy. It has been known that the orexinergic system has a significant role in mediating reward processing and addiction, as shown by the conditioned place preference (CPP). The dentate gyrus (DG) of the hippocampus receives orexinergic projections from the lateral hypothalamus that has been approved as a critical area arbitrating the maintenance of drug-seeking behavior following the extinction.

Cannabidiol modulates the METH-induced conditioned place preference through D2-like dopamine receptors in the hippocampal CA1 region.

The main problem with addiction is a relapse with a high rate in methamphetamine (METH) abusers. Using addictive drugs repetitively will cause the reward. METH reward is due to an increase in dopamine levels, and the endocannabinoid system (ECS) has a modulatory role in reward through CB1 receptors.