Chronic ethanol and withdrawal differentially modulate pre- and postsynaptic function at glutamatergic synapses in rat basolateral amygdala

J Neurophysiol. 2007 Dec;98(6):3185-96. doi: 10.1152/jn.00189.2007. Epub 2007 Sep 26.


Withdrawal anxiety is a significant factor contributing to continued alcohol abuse in alcoholics. This anxiety is long-lasting, can manifest well after the overt physical symptoms of withdrawal, and is frequently associated with relapse in recovering alcoholics. The neurobiological mechanisms governing these withdrawal-associated increases in anxiety are currently unknown. The basolateral amygdala (BLA) is a major emotional center in the brain and regulates the expression of both learned fear and anxiety. Neurotransmitter system alterations within this brain region may therefore contribute to withdrawal-associated anxiety. Because evidence suggests that glutamate-gated neurotransmitter receptors are sensitive to acute ethanol exposure, we examined the effect of chronic intermittent ethanol (CIE) and withdrawal (WD) on glutamatergic synaptic transmission in the BLA. We found that slices prepared from CIE and WD animals had significantly increased contributions by synaptic NMDA receptors. In addition, CIE increased the amplitude of AMPA-receptor-mediated spontaneous excitatory postsynaptic currents (sEPSCs), whereas only WD altered the amplitude and kinetics of tetrodotoxin-resistant spontaneous events (mEPSCs). Similarly, the frequency of sEPSCs was increased in both CIE and WD neurons, although only WD increased the frequency of mEPSCs. These data suggest that CIE and WD differentially alter both pre- and postsynaptic properties of BLA glutamatergic synapses. Finally, we show that microinjection of the AMPA-receptor antagonist, DNQX, can attenuate withdrawal-related anxiety-like behavior. Together, our results suggest that increased glutamatergic function may contribute to anxiety expressed during withdrawal from chronic ethanol.

Publication types

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

MeSH terms

  • Administration, Inhalation
  • Amygdala / drug effects*
  • Animals
  • Anxiety / chemically induced
  • Anxiety / psychology
  • Central Nervous System Depressants / pharmacology*
  • Data Interpretation, Statistical
  • Electrophysiology
  • Ethanol / pharmacology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Glutamates / physiology*
  • Male
  • Microinjections
  • Neurotransmitter Agents / metabolism
  • Patch-Clamp Techniques
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Substance Withdrawal Syndrome / physiopathology*
  • Synapses / drug effects*
  • Synaptic Transmission / drug effects*
  • Tetrodotoxin / pharmacology


  • Central Nervous System Depressants
  • Excitatory Amino Acid Antagonists
  • Glutamates
  • Neurotransmitter Agents
  • Quinoxalines
  • Receptors, N-Methyl-D-Aspartate
  • Ethanol
  • Tetrodotoxin
  • FG 9041