Chronic ethanol and withdrawal effects on kainate receptor-mediated excitatory neurotransmission in the rat basolateral amygdala.
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.
Läck
A K
AK
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Christian
D T
DT
Diaz
M R
MR
McCool
B A
BA
D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D001921:Brain / Q000473:pathology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004558:Electric Stimulation; D004594:Electrophysiology; D000431:Ethanol / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects; D018092:Kainic Acid Receptors / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects*
D000409:Alanine; D002492:Central Nervous System Depressants; D000431:Ethanol; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; C490221:UBP296