Ethanol as a general anesthetic: actions in spinal cord.
Ethanol, usually studied in relation to intoxication, is also capable of producing general anesthesia. The most common standard of anesthetic potency is the concentration which produces immobility in response to a noxious stimulus. This concentration will be referred to as the anesthetic concentration. Immobilization is a spinal effect. Ethanol effects were studied in spinal cord from 2-7-day-old rats at concentrations which included the anesthetic concentration in both adult rats (97 mM) and 6-7-day-old rats (235 mM). At neonatal but not adult anesthetic concentrations, ethanol depressed monosynaptic reflex amplitude (mediated by glutamate AMPA receptors + compound action potential). At both neonatal and adult anesthetic concentrations ethanol reversibly depressed the population excitatory postsynaptic potential (pEPSP) (glutamate AMPA and NMDA receptors), the slow ventral root potential (NMDA + metabotropic receptors), and the dorsal root potential (GABA(A) receptors, via glutamate-excited interneurons). Effects were greater on NMDA receptor-mediated components than on AMPA-receptor-mediated components of the pEPSP and greater on NMDA than on metabotropic receptor-mediated components of the slow ventral root potential. The profile of ethanol effects on spinal cord resembles that of inhalation general anesthetics. The results show that both AMPA and NMDA receptor-mediated transmission are sensitive to ethanol and that enhancement of GABAergic neurotransmission is overridden by depression of excitation to the interneurons. They provide no obvious explanation for ethanol's lower general anesthetic potency in the neonate.
Wong
S M
SM
Department of Anesthesia, Stanford University School of Medicine, CA 94305-5117, USA.
Fong
E
E
Tauck
D L
DL
Kendig
J J
JJ
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D018681:Anesthetics, General / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D000431:Ethanol / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D066298:In Vitro Techniques; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012023:Reflex, Monosynaptic / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013126:Spinal Nerve Roots / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018681:Anesthetics, General; D000431:Ethanol; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D010879:Piperazines; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid