Modulatory role of the mPFC orexin-2 receptors in the acquisition and expression in two paradigms of the natural- and drug-induced conditioned place preference in the rats.

The neuropeptide orexin/hypocretin regulates adaptive behaviors needed for survival, including food intake, sleep-wake regulation, mating, and maternal behavior. However, the orexinergic system plays a critical role in addictive behavior and promotes seeking and rewarding substances of abuse and palatable food. Plenty of orexin receptors exist in the medial prefrontal cortex (mPFC). The PFC input to the NAc mediates goal-directed behaviors such as seeking behavior and planning actions to obtain rewarding substances. This study investigated the role of mPFC orexin-2 receptors (Orx2Rs) in natural-and drug-reward-seeking behaviors. One hundred sixteen adult male Wistar rats received TCS OX2 29 (3, 10, and 30 nmol/0.5 µl DMSO 12%) as an Orx2R antagonist in the mPFC during the acquisition and expression phases of two different CPP paradigms, morphine- and food-induced CPP protocols. Findings demonstrated that intra-mPFC administration of Orx2R antagonist reduced the acquisition and expression of morphine- and food-induced CPP in the rats. However, blockades of Orx2Rs in the mPFC have more inhibitory effects in food-induced CPP than in morphine-induced CPP. In conclusion, this study proposes a differential involvement of mPFC Orx2Rs in the acquisition and expression phases of CPP, suggesting distinguishable behavioral effects between food and morphine reward models. However, further mechanistic studies are required to clarify the underlying neural substrates.