Prenatal exposure to morphine alters kinetic properties of NMDA receptor-mediated synaptic currents in the hippocampus of rat offspring

Yang, Shyh‐Chyun; Yang, Jung Mou; Wu, Jian Nan; Kao, Yu Hshun; Hsieh, Wen Ya; Chao, Chia-Chen; Tao, Pao‐Luh

doi:10.1002/1098-1063(2000)10:6<654::aid-hipo1003>3.0.co;2-t

Cited by 30 publications

(17 citation statements)

References 46 publications

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“…Morphine and/or DM were progressively increased at the rate of 1 mg/kg at 7-day intervals from a beginning dose of 2 mg/kg for both morphine and DM, as previously described (Yeh et al, 1995;Tao et al, 2001;Yang et al, 2000Yang et al, , 2003. The rats were mated between days 7 and 8.…”

Section: Animal Treatmentmentioning

confidence: 99%

“…Hippocampal slices were prepared from rat offspring from drug-treated or vehicle-control mothers, as described previously (Yang et al, 2000(Yang et al, , 2003(Yang et al, , 2004. The slices (300-350 lm) were cut transversely to the long axis of the hippocampus with a vibroslicer (Campden Instruments, Sileby, Loughboroug, UK) and were immediately transferred to the artificial cerebrospinal fluid (aCSF) in an incubating chamber provided with humidified 95% O 2 /5% CO 2 gas at RT.…”

Section: Slice Preparationmentioning

confidence: 99%

“…Bipolar stimulating electrodes (tip separation about 200 lm; WPI, Sarasota, FL) were positioned in Schaffer/commissural pathways at a distance within 100 lm from the cell body layer of CA1 pyramidal cells in order to stimulate mainly proximal apical dendritic synapses, thereby minimizing space-clamp errors and dendritic filtering (Yang et al, 2000(Yang et al, , 2003). The exposed tip diameter of the stimulating electrode was about 50 lm.…”

Section: Whole-cell Recordingsmentioning

confidence: 99%

“…In addition, the impairment in the sensitivity in morphine-induced analgesia (Friedler, 1974;O'Callaghan and Holtzman, 1976) and decrease in the susceptibility to bicuculline seizures (Schindler et al, 2001) were also observed in such offspring. We previously suggested that prenatal exposure to morphine altered hippocampal N-methyl-D-asparate receptor (NMDAR) channel kinetics in offspring at the age of postnatal days 14 (P14), the phosphorylation of cAMP responsive element-binding protein at serine-133 (CREB Serine-133 , an important NMDAR-activated transcription factor for mammalian learning and memory) with impaired performance of longterm learning and memory in offspring (Yang et al, 2000;. Moreover, the phosphorylation of CREB Serine-133 and induction of early response genes was blocked by NMDAR antagonists (Steiner and Kitai, 2000;Steward and Worley, 2001;Kelly, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Alterations of postsynaptic density proteins in the hippocampus of rat offspring from the morphine‐addicted mother: Beneficial effect of dextromethorphan

et al. 2006

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Infants passively exposed to morphine or heroin through their addicted mothers usually develop characteristic withdrawal syndrome of morphine after birth. In such early life, the central nervous system exhibits significant plasticity and can be altered by various prenatal influences, including prenatal morphine exposure. Here we studied the effects of prenatal morphine exposure on postsynaptic density protein 95 (PSD-95), an important cytoskeletal specialization involved in the anchoring of the NMDAR and neuronal nitric oxide synthase (nNOS), of the hippocampal CA1 subregion from young offspring at postnatal day 14 (P14). We also evaluated the therapeutic efficacy of dextromethorphan, a widely used antitussive drug with noncompetitive antagonistic effects on NMDARs, for such offspring. The results revealed that prenatal morphine exposure caused a maximal decrease in PSD-95 expression at P14 followed by an age-dependent improvement. In addition, prenatal morphine exposure reduced not only the expression of nNOS and the phosphorylation of cAMP responsive element-binding protein at serine 133 (CREB(Serine-133)), but also the magnitude of long-term depression (LTD) at P14. Subsequently, the morphine-treated offspring exhibited impaired performance in long-term learning and memory at later ages (P28-29). Prenatal coadministration of dextromethorphan with morphine during pregnancy and throughout lactation could significantly attenuate the adverse effects as described above. Collectively, the study demonstrates that maternal exposure to morphine decreases the magnitude of PSD-95, nNOS, the phosphorylation of CREB(Serine-133), and LTD expression in hippocampal CA1 subregion of young offspring (e.g., P14). Such alterations within the developing brain may play a role for subsequent neurological impairments (e.g., impaired performance of long-term learning and memory). The results raise a possibility that postsynaptic density proteins could serve an important role, at least in part, for the neurobiological pathogenesis in offspring from the morphine-addicted mother and provide tentative therapeutic strategy.

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Section: Animal Treatmentmentioning

confidence: 99%

Section: Slice Preparationmentioning

confidence: 99%

Section: Whole-cell Recordingsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Alterations of postsynaptic density proteins in the hippocampus of rat offspring from the morphine‐addicted mother: Beneficial effect of dextromethorphan

et al. 2006

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“…Because morphine is reported to alter protein expression and functional property of NMDA receptors in vivo (Inoue et al, 2003; Ma et al, 2007; Yang et al, 2000) which may change the intracellular concentration of Ca 2+ , we evaluated the participation of NMDA receptor in morphine-regulated calcineurin activity and GluR1-S845 dephosphorylation. DL-APV (100 µM), a NMDA receptor antagonist, was applied one hour prior to treatment with morphine.…”

Section: Resultsmentioning

confidence: 99%

Morphine Induces AMPA Receptor Internalization in Primary Hippocampal Neurons via Calcineurin-Dependent Dephosphorylation of GluR1 Subunits

Kam¹,

Liao²,

Loh³

et al. 2010

J. Neurosci.

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Chronic morphine treatment resulting in the alteration of postsynaptic levels of AMPA receptors, thereby modulating synaptic strength, has been reported. However, the mechanism underlying such drug-induced synaptic modification has not been resolved. By monitoring the GluR1 trafficking in primary hippocampal neurons using the pHluorin-GluR1 imaging and biotinylation studies, we observed that prolonged morphine exposure significantly induced loss of synaptic and extrasynaptic GluR1 by internalization. The morphine-induced GluR1 endocytosis was independent of neural network activities or NMDA receptor activities, as neither blocking the sodium channels with tetrodotoxin nor NMDA receptors with DL-APV altered the effects of morphine. Instead, morphine-induced GluR1 endocytosis is attributed to a change in the phosphorylation state of the GluR1 at Ser 845 as morphine significantly decreased the dephosphorylation of GluR1 at this site. Such changes in Ser 845 phosphorylation required morphine-induced activation of calcineurin, based on the observations that a calcineurin inhibitor, FK506, completely abrogated the dephosphorylation, and morphine treatment led to an increase in calcineurin enzymatic activity, even in the presence of DL-APV. Importantly, pretreatment with FK506 and overexpression of the GluR1 mutants, S845D (phospho-mimic) or S845A (phospho-blocking) attenuated the morphine-induced GluR1 endocytosis. Therefore, the calcineurin-mediated GluR1-S845 dephosphorylation is critical for the morphine-induced changes in the postsynaptic AMPA receptor level. Together, these findings reveal a novel molecular mechanism for opioid-induced neuronal adaptation and/or synaptic impairment.

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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

Yang¹,

Huang²,

Wang³

et al. 2003

Hippocampus

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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 (CREBSerine-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 CREBSerine-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 CREBSerine-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.

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Prenatal exposure to morphine alters kinetic properties of NMDA receptor-mediated synaptic currents in the hippocampus of rat offspring

Cited by 30 publications

References 46 publications

Alterations of postsynaptic density proteins in the hippocampus of rat offspring from the morphine‐addicted mother: Beneficial effect of dextromethorphan

Alterations of postsynaptic density proteins in the hippocampus of rat offspring from the morphine‐addicted mother: Beneficial effect of dextromethorphan

Morphine Induces AMPA Receptor Internalization in Primary Hippocampal Neurons via Calcineurin-Dependent Dephosphorylation of GluR1 Subunits

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

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Prenatal exposure to morphine alters kinetic properties of NMDA receptor-mediated synaptic currents in the hippocampus of rat offspring

Cited by 30 publications

References 46 publications

Alterations of postsynaptic density proteins in the hippocampus of rat offspring from the morphine‐addicted mother: Beneficial effect of dextromethorphan

Alterations of postsynaptic density proteins in the hippocampus of rat offspring from the morphine‐addicted mother: Beneficial effect of dextromethorphan

Morphine Induces AMPA Receptor Internalization in Primary Hippocampal Neurons via Calcineurin-Dependent Dephosphorylation of GluR1 Subunits

Prenatal administration of morphine decreases CREBSerine‐133 phosphorylation and synaptic plasticity range mediated by glutamatergic transmission in the hippocampal CA1 area of cognitive‐deficient rat offspring

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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