Morphine could increase apoptotic factors in the nucleus accumbens and prefrontal cortex of rat brain's reward circuitry

• Apoptotic factors were increased after development of morphine rewarding effects.
• Morphine increased the Bax/Bcl2 ratio, caspase3 and PARP levels in the NAc.
• Morphine increased the Bax/Bcl2 ratio, caspase3 and PARP levels in the PFC.
• The maximum change in apoptotic factors appeared with low dose morphine in the NAc.
• The maximum change in apoptotic factors appeared with effective morphine in the PFC.

The nucleus accumbens (NAc) and prefrontal cortex (PFC) are two parts of neuronal reward circuit involved in motivated and goal-directed behaviors. Some data suggest that morphine is toxic to neurons and induces apoptosis, while other evidence shows that morphine could have beneficial effects against cell death. This study was designed to evaluate the effect of morphine on apoptosis by measuring the expression of apoptotic proteins in two important regions, the NAc and PFC, in the rat brain's reward circuitry. Morphine subchronic administration in different doses (0.5, 5 and 10 mg/kg) in conditioned place preference (CPP) paradigm (3 times in 3 days, for each dose in each group of rats) was used to induce its rewarding effect. Then, the expression of four apoptotic factors; Bax, Bcl2, caspase3 and PARP, in the NAc and PFC were assessed using the Western blot technique. All of morphine-treated groups showed increase of apoptotic factors in these regions. In the NAc, morphine significantly increased the Bax/Bcl-2 ratio, caspase3 and PARP in the lowest dose (0.5 mg/kg) but in the PFC considerable increase was seen in dose of 5 mg/kg. Elevation of apoptotic factors in the NAc and PFC implies that morphine can affect the molecular mechanisms which interfere with apoptosis through different receptors. Our findings suggest that the NAc and PFC may have a different distribution of receptors which become active in different doses of morphine.