| Summary: | 碩士 === 台北醫學院 === 醫學研究所 === 86 === Children born to morphine or heroin addicted mothers have been shown to suffer
acute withdrawal syndrome after birth and develop a long-term neuropsychologi
cal sequels. Considerable evidences have confirmed that prenatal exposure to m
orphine also produce significant alteration in developing brain including reta
rdation in neurite growth, change in neurotransm?揶r release and the expressi
on of receptors. Our previous study has shown that combined prenatal- and post
-natal exposure to morphine induced an age-dependent decrease in the density o
f the N-methyl-D-aspartate (NMDA) receptor in the developing rat brain. To fur
ther explore the region-specificity of this alteration in the ontogeny of the
NMDA receptor I used [3H] [1(2-thienyl)-cyclohexyl]3,4-piperidine ([3H]-TCP) ,
a ligand that bound to NMDA receptor-coupled ion channel, to quantify the den
sities of NMDA receptor on the crude membrane prepared from cortex, hippocamp
us and striatum of rats born to dams rats received chronic treatment of morphi
ne. I found that morphine group rats have a density of the NMDA receptor in co
rtex and hippocampus 23.7% and 26.8% lower than that of control groups on post
natal day (PND) 14 only but not on other examined PND. However, no significant
difference between these two group of rats in striatum was found. I further d
etermined whether alteration in the ontogeny of the NMDA receptor will alter t
he excitability of brain, I used kainic acid (KA) to induce seizure behavior i
n both control and morphine group rats as a parameter in reflecting the excita
bility in these brains. The result showed that morphine rats presented an incr
eased sensitivity to KA on PND 14 but on other examined PND. I further determi
ned the effect of dextromethorphan (DM), an NMDA receptor channel blocker, in
attenuating naloxone-precipitated withdrawal syndrome, manifested as abdominal
stretching, in morphine group rats. The result showed that DM with dose of 20
or 30 mg/kg subcutaneous injection decreased the frequency and latency of nal
oxone-induced abdominal stretching of morphine group rats on PND 7. These resu
lts suggested that prenatal and post-natal morphine exposure will induce alter
ation in a age-dependent and region-dependent alteration in the ontogeny of th
e NMDA receptor and brain excitability. Whether this alteration will bring imp
act on the development of normal brain functions required further investigatio
n.
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