Functional characterization of a kindling-like model of ethanol withdrawal in cortical cultured neurons after chronic intermittent ethanol exposure

Xian Jue Hu, Maharaj K. Ticku

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Chronic ethanol exposure has been reported to alter NMDA and GABA(A) receptor function and gene expression in brain regions of animals and mammalian cultured conical neurons. In the present study, we investigated the effects of another model of chronic, but intermittent, ethanol treatment (CIE) on GABA(A) and NMDA receptor systems in conical neurons. CIE (50 mM ethanol, 12 h exposure/12 h withdrawal, 5 cycles) exposure produced increased [3H]MK-801 binding and diazepam insensitive binding sites as measured by [3H]Ro15-4513 binding to conical cultured neuronal membranes, at 0 h following the last treatment cycle relative to control neurons. The NMDA mediated increase in intracellular calcium [Ca2+](i) was also increased following similar CIE treatment. CIE treatment also increased the ability of pentylenetetrazol (PTZ) to inhibit GABA mediated 36Cl- influx relative to control neurons. These effects were not reversible following 1 week ethanol withdrawal, implying enhanced sensitivity of PTZ to inhibit GABA(A) receptor mediated inhibition, and an increased NMDA receptor function in CIE treated cortical neurons. These alterations are consistent with the behavioral studies in animals, and suggest that both GABA(A) and NMDA receptors play an important role in ethanol withdrawal following either chronic or CIE exposure. Furthermore, this provides a feasible in vitro model for further biochemical and molecular studies of the mechanism underlying the CIE induced kindling-like phenomenon observed in humans.

Original languageEnglish (US)
Pages (from-to)228-234
Number of pages7
JournalBrain Research
Volume767
Issue number2
DOIs
StatePublished - Sep 5 1997

Keywords

  • Cl influx
  • Chronic intermittent ethanol (CIE)
  • Intracellular free calcium
  • Kindling
  • MK-801
  • Ro15-4513

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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