| Alterations of postsynaptic density proteins in the hippocampus of rat offspring from the morphine-addicted mother: Beneficial effect of dextromethorphan. | |
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MedLine Citation:
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PMID: 16598705 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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San Nan Yang; Chieh-An Liu; Mei-Yung Chung; Hsin-Chun Huang; Geng-Chang Yeh; Chih-Shung Wong; Wei-Wen Lin; Chun-Hua Yang; Pao-Luh Tao |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Hippocampus Volume: 16 ISSN: 1050-9631 ISO Abbreviation: Hippocampus Publication Date: 2006 |
Date Detail:
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Created Date: 2006-06-05 Completed Date: 2006-07-27 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9108167 Medline TA: Hippocampus Country: United States |
Other Details:
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Languages: eng Pagination: 521-30 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, Chang-Gung Memorial Hospital, Kaohsiung, Taiwan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Cyclic AMP Response Element-Binding Protein / drug effects, metabolism Dextromethorphan / pharmacology*, therapeutic use Disease Models, Animal Excitatory Amino Acid Antagonists / pharmacology, therapeutic use Female Hippocampus / drug effects*, metabolism, physiopathology Intracellular Signaling Peptides and Proteins / drug effects*, metabolism Long-Term Synaptic Depression / drug effects, physiology Membrane Proteins / drug effects*, metabolism Morphine / adverse effects* Morphine Dependence / complications* Narcotics / adverse effects Neuronal Plasticity / drug effects, physiology Nitric Oxide Synthase Type I / drug effects, metabolism Organ Culture Techniques Phosphorylation / drug effects Pregnancy Prenatal Exposure Delayed Effects / drug therapy, metabolism*, physiopathology Rats Rats, Sprague-Dawley Receptors, N-Methyl-D-Aspartate / drug effects, metabolism Synaptic Membranes / drug effects, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Cyclic AMP Response Element-Binding Protein; 0/Dlgh4 protein, rat; 0/Excitatory Amino Acid Antagonists; 0/Intracellular Signaling Peptides and Proteins; 0/Membrane Proteins; 0/Narcotics; 0/Receptors, N-Methyl-D-Aspartate; 125-71-3/Dextromethorphan; 57-27-2/Morphine; EC 1.14.13.39/Nitric Oxide Synthase Type I |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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