| Summary: | 碩士 === 台北醫學院 === 醫學研究所 === 90 === Prenatal exposure to morphine introduces a variety of alteration in the developing rat brain. Our previous studies had revealed that rat born to dams rat, which had chronically received morphine treatment during gestation and lactation period, had abnormal expression of the N-methyl-D-aspartate (NMDA) receptor in the brain during developing stage. I further determined whether the expression of AMPA receptor, one subtype receptor of the non-NMDA glutamate receptor, and Ca2+ calcium/camodulin dependent kinase II (CaMKII) are also altered. The immunoblotting studies showed that the abundance of AMPA receptor subunit proteins, namely GluR1, GluR3 and GluR4, in the rats born to morphine-treated dam rats (Group I) was significantly lower than that of rats born to saline-treated dam rats (control group) on postnatal day (PND) 7 and PND14. However, Such change is region-specific. This study suggested that prenatal exposure to morphine induced a quantitative and qualitative alteration in the AMPA receptor, which may further alter the AMPA receptor-mediated neurophysiological responses in the developing brain. Furthermore, the study of the CaMKII activity in the hippocampus showed that both the endogenous NMDA receptor-mediated Ca2+/camoduline dependent or independent CaMKII kinase activity of morphine group was not different to that of control group on all examined PND. However, both the kainic acid(KA)—induced NMDA receptor-Mediated Ca2+/camoduline dependent or independent CaMKII kinase activity of morphine group rats was significantly lower than that of control group rats on all examined PND. Correlated well with this study is the finding that KA-induced NMDA receptor-mediated phosphorelated CaMKII of morphine group was also lower than that of control group. This result indicated that the down-regulation of the NMDA receptor in the developing rats brain induced by prenatal exposure to morphine has significantly influence the NMDA receptor-mediated biochemical cascade, which is important for the maturation for the brain function.
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