Effect of morphine on apoptotic factors caspase-3, PARP and Bax/Bcl-2 ratio in nucleus accumbens in conditioned place preference model in rat

Introduction: Nucleus accumbens (NAc) plays a critical role in neuronal reward circuits that are responsible for motivated and goal-directed behaviors. Some data suggest that morphine induces apoptosis in neurons, while other evidences show that morphine could have beneficial effects against neuronal cell death. This study was designed to evaluate the effect of morphine on apoptosis in the NAc in rat brain by assessing the changes in apoptotic factors. Methods: To investigate the effects of 3 different doses (0.5, 5 and 10 mg/kg) of morphine on induction of apoptotic factors in the NAc after its sub-chronic consumption, conditioned place preference paradigm was used in three groups of rats compared with the control group that received saline, and then the changes in apoptotic factors caspase-3, PARP and Bax/Bcl-2 ratio were assessed by western blot technique. Results: Our results showed that apoptotic factors increase in all three groups treated with morphine. In the nucleus accumbens, morphine induced significant increase (p<0.01) in caspase-3, PARP and Bax/Bcl-2 ratio, in the lowest dose (0.5 mg/kg) compared with the control group that received saline instead of morphine. Conclusion: Increase in apoptotic factors by low dose morphine in the nucleus accumbens of morphine-treated rats shows that morphine can affect the molecular mechanisms which interfere with apoptosis through one kind of its receptors with high affinity. However, with increase in dose of morphine, it seems that other kinds of opioid receptors have been involved which exert some neuroprotective effects of morphine against apoptosis.