Chronic Morphine Exposure Enhanced NMDA Receptor-Mediated Cytotoxicity in Primary Cortical Cells

Infants of morphine-addicted mothers had a higher incidence of neonatal abstinence syndrome and retardation in neurobiological development. Chronic treatment of morphine in pregnant rats changed the number of NMDA receptors in the hippocampus of their offspring. Our previous study indicated that chronic morphine exposure enhanced NMDA receptor-mediated functions in the central nervous system (CNS) of morphine-addicted rats. However, it remains unclear whether chronic morphine exposure could enhance NMDA induced cytotoxicity in the CNS. In this study, we evaluated whether chronic morphine exposure enhanced NMDA induced cytotoxicity in primary mixed cortical cells of rats. Results indicated that morphine (10^(-4)-10^(-2) M) or NMDA (30-1000 uM) addition concentration- dependently produced cytotoxicity. Furthermore, chronic pretreatment of morphine exposure could potentiate NMDA induced cytotoxicity. In conclusion, the results here demonstrated that cytotoxicity was synergistically induced by NMDA in the presence of chronic morphine exposure. It seemed that nitric oxide did not play an important role for this synergistic cytotoxicity. However, it is likely that chronic morphine exposure modulated NMDA receptor-mediated functions, such as an increase of Ca^(2+) influx, and hence activated pathological mechanisms leading to this synergistic cytotoxicity.