Changes in apoptotic factors caspase-3, PARP and Bax/Bcl-2 ratio in the ventral tegmental area after the acquisition and extinction of morphine-induced conditioned place preference in the rat

 Introduction: Chronic high doses of morphine inhibit cell proliferation and induce cell death. One of the centers in reward pathway is the ventral tegmental area (VTA). Stimulation of opioid receptors in the reward circuit in the brain by morphine could be enabling a factor induce apoptosis in some brain regions, and expression of death receptors increases on the cell surface. This study was designed to evaluate the effect of morphine on changes in apoptotic factors (Bax/Bcl-2, PARP and caspase-3) in the VTA during the acquisition of morphine-induced conditioned place preference (CPP) and extinction period.  Materials and Methods: In this study, in behavioral experiments, the CPP paradigm was done on 64 adult male albino Wistar rats. In saline-control and three doses of morphine (0.5, 5, 10 mg/kg) experimental groups in acquisition, in addition with effective dose of morphine (5 mg/kg) evaluate extinction period (8 days). Then, in the molecular section the changes in apoptotic proteins assess with western blot technique. Results: We found that apoptotic factors increase in all three experimental groups in response to morphine. However, the most response was significantly occurred at the dose of 5 mg/kg morphine. Additionally, there is no change has been seen in the apoptotic factors during the extinction period.  Conclusion: It seems that morphine in all doses cause apoptosis, but quite contrary, by increasing the dose of morphine, the number of receptors involved in apoptosis increases and morphine’s neuroprotective effects are appeared.