Chronic ethanol and withdrawal effects on kainate receptor-mediated excitatory neurotransmission in the rat basolateral amygdala

Alcohol. 2009 Feb;43(1):25-33. doi: 10.1016/j.alcohol.2008.11.002.


Withdrawal (WD) anxiety is a significant factor contributing to continued alcohol abuse in alcoholics. This anxiety is extensive, long-lasting, and develops well after the obvious physical symptoms of acute WD. The neurobiological mechanisms underlying this prolonged WD-induced anxiety are not well understood. The basolateral amygdala (BLA) is a major emotional center in the brain and regulates the expression of anxiety. New evidence suggests that increased glutamatergic function in the BLA may contribute to WD-related anxiety following chronic ethanol exposure. Recent evidence also suggests that kainate-type ionotropic glutamate receptors are inhibited by intoxicating concentrations of acute ethanol. This acute sensitivity suggests potential (KA-R) contributions by these receptors to the increased glutamatergic function seen during chronic exposure. Therefore, we examined the effect of chronic intermittent ethanol (CIE) and WD on KA-R-mediated synaptic transmission in the BLA of Sprague-Dawley rats. Our study showed that CIE, but not WD, increased synaptic responses mediated by KA-Rs. Interestingly, both CIE and WD occluded KA-R-mediated synaptic plasticity. Finally, we found that BLA field excitatory postsynaptic potential responses were increased during CIE and WD via a mechanism that is independent of glutamate release from presynaptic terminals. Taken together, these data suggest that KA-Rs might contribute to postsynaptic increases in glutamatergic synaptic transmission during CIE and that the mechanisms responsible for the expression of KA-R-dependent synaptic plasticity might be engaged by chronic ethanol exposure and WD.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alanine / analogs & derivatives
  • Alanine / pharmacology
  • Amygdala / drug effects*
  • Animals
  • Brain / pathology
  • Central Nervous System Depressants / pharmacology*
  • Electric Stimulation
  • Electrophysiology
  • Ethanol / pharmacology*
  • Excitatory Postsynaptic Potentials / drug effects
  • Male
  • Neuronal Plasticity / drug effects
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glutamate / drug effects
  • Receptors, Kainic Acid / drug effects*
  • Substance Withdrawal Syndrome / physiopathology*
  • Synaptic Transmission / drug effects*


  • Central Nervous System Depressants
  • Receptors, Glutamate
  • Receptors, Kainic Acid
  • UBP296
  • Ethanol
  • Alanine