Glutamate receptor-mediated hyperexcitability after ethanol exposure in isolated neonatal rat spinal cord.
This study examined the mechanism for hyperexcitability after ethanol withdrawal from isolated neonatal rat spinal cord. Ethanol (65-130 mM, 30 min) significantly depressed the glutamate receptor-mediated population excitatory postsynaptic potential (pEPSP) underlying the monosynaptic reflex. On washing with drug-free solution the response recovered to levels significantly above control. Minimum ethanol exposure time required for induction of withdrawal hyperexcitability was approximately 15 min. A second application of ethanol after washout depressed the pEPSP to an extent similar to the first, and a second wash did not elevate response significantly more than the initial wash. Ethanol-induced hyperexcitability thus develops with a time course of minutes and plays a role in determining apparent initial ethanol potency. Both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and N-methyl-D-aspartate receptor-mediated components of the pEPSP were necessary for the expression of hyperexcitability on withdrawal but not for its induction. Butanol withdrawal also was associated with hyperexcitability, methanol was not. The case with octanol is uncertain because of slow recovery from this more lipophilic agent. Hyperexcitability on ethanol withdrawal was specific to the glutamate receptor-mediated pEPSP and not generalized to other evoked potentials. These results may be relevant to rapid and/or very rapid acute functional tolerance and to ethanol withdrawal.
Wong
S M
SM
Department of Anesthesia, Stanford University School of Medicine, Stanford, California 94305, USA.
Tauck
D L
DL
Fong
E G
EG
Kendig
J J
JJ
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D005260:Female; D008297:Male; D051381:Rats; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000378:metabolism; D013116:Spinal Cord / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology
D002492:Central Nervous System Depressants; D017470:Receptors, Glutamate; D000431:Ethanol