Chronic ethanol treatment upregulates the NMDA receptor function and binding in mammalian cortical neurons

Xian Jue Hu, Maharaj K. Ticku

Research output: Contribution to journalArticlepeer-review

148 Scopus citations

Abstract

In the present study, we investigated the effects of chronic ethanol exposure on NMDA-mediated increase in intracellular calcium concentration ([Ca2+]i) by means of fluorescent measurement of [Ca2+]i with Fura-2AM in mammalian cortical cultured neurons, and the radioligand [3H]MK-801 binding to cortical neuronal membranes. Chronic exposure of the cortical neurons to ethanol (50 mM, 5 days) did not produce any change in the cell protein, morphological appearance, and the resting [Ca2+]i; however, it significantly enhanced the NMDA-mediated increase in [Ca2+]i. The EC50 value of NMDA was not significantly altered following chronic ethanol exposure, however, its Emax value was increased by ∼ 45%. Furthermore, chronic ethanol exposure increased the specific [3H]MK-801 binding in cortical neuronal membrane preparation by ∼ 30%. The enhancement of the NMDA-mediated increase in [Ca2+]i and the increase in [3H]MK-801 specific binding were reversed following 48 h ethanol withdrawal. Additionally, this enhanced NMDA response and the increased [3H]MK-801 specific binding were susceptible to blockade by the concomitant chronic exposure of the cortical neurons to the NMDA receptor competitive (20 μM CPP), and non-competitive (1 μM MK-801) antagonists, but not by the non-NMDA receptor antagonist, CNQX (10 μM), and the L-type calcium channel blocker, nitrendipine (10 μM). Taken together, these results suggest that chronic ethanol exposure upregulated the NMDA receptor function and binding in cortical cultured neurons, and this increased NMDA receptor function is a NMDA receptor-mediated process. This altered NMDA receptor function may be responsible for the chronic ethanol-induced behavioral consequences and withdrawal syndrome associated with chronic ethanol exposure.

Original languageEnglish (US)
Pages (from-to)347-356
Number of pages10
JournalMolecular Brain Research
Volume30
Issue number2
DOIs
StatePublished - Jun 1995

Keywords

  • Ca
  • Cortical neuron
  • Ethanol
  • NMDA receptor
  • Upregulation

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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