Ethanol concentrations approaching minimum alveolar anesthetic concentration are required to suppress learning in a fear-potentiated startle paradigm in rats.
We previously demonstrated that desflurane and two nonimmobilizers dose-dependently decrease learning and memory in rats. This suggests that although they do not suppress movement in response to noxious stimuli, nonimmobilizers act like inhaled anesthetics in their effects on learning and memory. Like most conventional anesthetics, nonimmobilizers have a greater affinity for lipid than for aqueous phases. In the present study, we examined the effect of ethanol on learning and memory to test the hypothesis that a large part of the capacity of anesthetics to affect learning depends on an action on a lipid (nonpolar) phase. Unlike volatile anesthetics and nonimmobilizers, ethanol has a greater affinity for water than for lipids. Thus, if our hypothesis is correct, ethanol should be relatively less potent in its suppression of memory. Rats receiving various doses of ethanol were conditioned to fear a light followed by a footshock. Fear conditioning to the light was subsequently assessed by measurement of potentiation of the acoustic startle reflex in the presence, compared with the absence, of light. Ethanol up to 0.54 minimum alveolar anesthetic concentration (MAC) did not abolish fear, but 0.82 MAC ethanol did abolish learning. Expressed as a fraction of MAC or predicted MAC, ethanol is less potent than desflurane or the nonimmobilizer 1,2-dichlorohexafluorocyclobutane in suppressing learning. This finding is consistent with the hypothesis that the capacity of anesthetics and nonimmobilizers to impair learning and memory depends mostly on an action at a nonpolar site.


CONCLUSIONS
Abolition of learning and memory is an important property of inhaled anesthetics. This effect primarily results from an action at a lipid (nonpolar) site, rather than a polar site or a water-lipid interface.
Sonner
J M
JM
Department of Anesthesia, University of California San Francisco, 94143-0464, USA. jim_sonner@quickmail.ucsf.edu
Li
J
J
Kandel
L
L
Eger
E I
EI
D018685:Anesthetics, Inhalation / Q000032:analysis; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000032:analysis / Q000494:pharmacology*; D005239:Fear; D007858:Learning / Q000187:drug effects*; D008297:Male; D011650:Pulmonary Alveoli / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*
D018685:Anesthetics, Inhalation; D002492:Central Nervous System Depressants; D000431:Ethanol