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

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

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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 (CREBSerine-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 CREBSerine-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.

Original languageEnglish
Pages (from-to)521-530
Number of pages10
JournalHippocampus
Volume16
Issue number6
DOIs
Publication statusPublished - 2006

Fingerprint

Dextromethorphan
Morphine
Hippocampus
Mothers
Nitric Oxide Synthase Type I
Long-Term Memory
Serine
Carrier Proteins
Phosphorylation
postsynaptic density proteins
Learning
Antitussive Agents
Maternal Exposure
Postpartum Depression
Heroin
Lactation
Central Nervous System
Parturition
Depression

Keywords

  • Creb
  • LTD
  • NMDA receptor
  • NOS
  • Opiate addiction
  • PSD-95

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Alteration of postsynaptic density proteins in the hippocampus of rat offspring from the morphine-addicted mother : Beneficial effect of dextromethorphan. / Yang, San Nan; Liu, Chieh An; Chung, Mei Yung; Huang, Hsin Chun; Yeh, Geng Chang; Wong, Chih Shung; Lin, Wei Wen; Yang, Chun Hua; Tao, Pao Luh.

In: Hippocampus, Vol. 16, No. 6, 2006, p. 521-530.

Research output: Contribution to journalArticle

Yang, San Nan ; Liu, Chieh An ; Chung, Mei Yung ; Huang, Hsin Chun ; Yeh, Geng Chang ; Wong, Chih Shung ; Lin, Wei Wen ; Yang, Chun Hua ; Tao, Pao Luh. / Alteration of postsynaptic density proteins in the hippocampus of rat offspring from the morphine-addicted mother : Beneficial effect of dextromethorphan. In: Hippocampus. 2006 ; Vol. 16, No. 6. pp. 521-530.
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