| Summary: | 碩士 === 臺北醫學大學 === 醫學研究所 === 92 === Part I
Our previous investigation revealed that rats born to dam rats chronically received morphine injection (morphine group rats) had a significant down-regulation of NMDA receptor in the hippocampus on postnatal day (PND) 14, but not on other examined PND. We further determined whether this down-regulation is specific for one of the subunit of NMDA receptor by using immunoblotting assay. The result showed that the NR2A, but not NR1 or NR2B, of morphine group rat was down-regulated on PND14, but not on PND30 or PND60 in the hippocampus of morphine group rats as compared to that of control rats. It is known that NR2A are linked to the anchoring protein, PSD95, on the post-synaptic density. However, we found that no change in the PSD-95 is associated with the down-regulation of NR2A. In addition, prenatal morphine treatment did not alter the expression of synaptophysin, a synaptic vesicle transmembrane protein in pre-synapse. To summary, these results demonstrated a transient down regulation of NR2A which is not associated with a change in the expression of PSD-95 and synaptophysin in the hippocampus of morphine group rats. Whether this early event in receptor alteration may hamper the development of neural function of hippocampus, such as learning and memory, in a long run require further explored.
Part II
It has been reported that infants born to morphine or heroin addicted women have high incidence of neonatal abstinence syndrome and abnormal neuropsychological performance. Previous studies had indicated that fluoxetine increasing serotonin (5-hydroxytryptamine, 5HT) transmission will attenuate morphine-induced locomotion and block morphine-sensitization. It is well-known that fluoxetine is a serotonin reuptake transpoter (SERT) inhibiter commonly used as antidepressants in clinics. In this study, we investigate the effect of fluoxetine and another two SERT inhibitors, citalopram and clomipramine, in attenuating naloxone precipitated-morphine withdraw syndrome in 5-day-old rats born to dams rats prenatally received daily morphine injections until 5 days post-delivery. Our data showed that fluoxetine、 clomipramine and citalopram can significantly increase latency of abdomen stretching, decrease frequency of abdomen stretching and yawn behavior in a dose-dependent manner in neonatal rats prenatally expose to morphine. This result suggests that SERT inhibitors could be of potential in clinics for treat in the acute morphine withdraw syndrome in newborn baby.
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