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Prenatal administration of morphine decreases CREB Serine‐133 phosphorylation and synaptic plasticity range mediated by glutamatergic transmission in the hippocampal CA1 area of cognitive‐deficient rat offspring
Author(s) -
Yang San Nan,
Huang LiTung,
Wang ChihLu,
Chen WuFu,
Yang ChinHwa,
Lin ShinnZong,
Lai MinChi,
Chen ShyiJao,
Tao PaoLuh
Publication year - 2003
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.10137
Subject(s) - offspring , long term potentiation , synaptic plasticity , nmda receptor , hippocampus , creb , neuroscience , glutamatergic , ampa receptor , glutamate receptor , hippocampal formation , endocrinology , medicine , chemistry , morris water navigation task , psychology , biology , receptor , transcription factor , pregnancy , biochemistry , genetics , gene
The central nervous system (CNS) exhibits remarkable plasticity in early life and can be altered significantly by various prenatal influences. We previously showed that prenatal exposure to morphine altered kinetic properties of N‐methyl‐ D ‐aspartate (NMDA) receptor‐mediated synaptic currents in the hippocampus of young rat offspring at the age of 14 days (P14). The present study further investigates whether NMDA receptor‐mediated synaptic plasticity and/or cyclic adenosine monophosphate‐responsive element‐binding protein (CREB Serine‐133 ), an important transcription factor underlying learning and memory, can be altered by prenatal morphine exposure in these offspring. Subsequently, the Morris water maze task was performed at the older ages (P28‐P31). The magnitude of long‐term depression (LTD) generated by a low‐frequency stimulation (LFS, 1 Hz for 15 min) in hippocampal slices from the vehicle‐control offspring (P14) was significantly larger than that in slices from the morphine‐treated offspring, although there was no such difference in the magnitude of long‐term potentiation (LTP) elicited by a high‐frequency stimulation (100 Hz for 1 s) between the two groups. Comparison of the expression range of glutamatergic synaptic plasticity in slices from the vehicle‐control and morphine‐treated offspring, calculated as the difference in the maximal magnitude between LTP and LTD, demonstrated a remarkably smaller range in the slices from the morphine‐treated offspring. In addition, the decreased phosphorylation of CREB Serine‐133 and the impaired ability of spatial learning were also seen in the morphine‐treated offspring, as compared with the vehicle‐control offspring. Collectively, the study suggests that maternal exposure to morphine reduces the range of synaptic plasticity by decreasing the expression of LTD, but not of LTP, in CA1 pyramidal neurons of the hippocampus from rat offspring. More importantly, decreased phosphorylation of CREB Serine‐133 may play a role for the impaired spatial learning and memory in rat offspring exposure to prenatal morphine. Thus, the findings here may provide important insights into cellular/molecular mechanisms underlying pathophysiological changes in the CNS of young offspring from morphine‐addicted mothers and serve as a basis for possible therapeutic intervention. © 2003 Wiley‐Liss, Inc.