Augmentation of morphine-conditioned place preference by food restriction is associated with alterations in the oxytocin/oxytocin receptor in rat models

Background: Studies indicate that food restriction (FR) reinforces the effects of morphine. The exact mechanisms by which FR influences the reward circuitry of morphine have not yet been determined. Objectives: We hypothesized that the effects of FR on the oxytocin (OXT) system and HPA axis can be associated with substance abuse disorders. In this study, the serum levels of OXT and corticosterone, and the expression of OXT/OXT receptor (OXTR), glucocorticoid receptor (GR), and brain-derived neurotrophic factor (BDNF) in the hippocampus, prefrontal cortex, and nucleus accumbens were investigated in an FR model. Methods: First, the male rats (n?=?8 per group) were subjected to FR for 3?weeks. Then, morphine-induced conditioned place preference (CPP) was observed using two doses of morphine (3 and 5 mg/kg). The serum concentrations of corticosterone and OXT were determined by ELISA and the expression of genes was examined by qPCR. Results: FR induced an enhanced preference in the animals for the 5 mg/kg dose of morphine compared to the controls. Serum corticosterone levels increased after FR but OXT levels decreased. Meanwhile, FR actuated downregulation of GR, BDNF, and OXT genes, while inducing the overexpression of OXTR. Conclusion: We propose the inclusion of OXT and OXTR alterations in the enhancement of morphine-induced CPP and addiction vulnerability following FR. Moreover, we conclude that altered BDNF levels and HPA axis activity may be the mechanisms involved in the effects of FR on morphine-induced behavior.