title: Desflurane and the nonimmobilizer 1,2-dichlorohexafluorocyclobutane suppress learning by a mechanism independent of the level of unconditioned stimulation.
abstract: We previously demonstrated that anesthetics and non-immobilizers suppress learning and memory in rats. In the training portion of the test, rats received a light plus a footshock and learned to associate the two, as evidenced by subsequent potentiation of the response (jumping) to light plus a noise (fear-potentiated startle). However, anesthetics and nonimmobilizers also decreased the response of animals receiving footshocks during training, which suggests that the reduction in fear-potentiated startle might reflect analgesia, rather than an impairment of learning and memory. Furthermore, although we previously demonstrated that the nonimmobilizer 2,3-dichlorohexafluorocyclobutane (2N) could completely abolish learning, we did not demonstrate the minimal dose required. In the present study, we eliminated analgesia as a confounding factor by training rats breathing desflurane and 2N with footshock intensities that produced responses at least equal to those produced in control animals. Both desflurane and 2N suppressed learning at 0.2 times the minimum alveolar anesthetic concentration (MAC) or the MAC predicted from lipid solubility, despite the increased footshock intensity. This partial pressure of desflurane equals that previously shown to suppress learning at lower footshock intensities. We conclude that suppression of learning and memory by desflurane and 2N does not result from decreased sensitivity to the unconditioned stimulus (the footshock) and that the potency of 2N is consistent with its lipophilicity.
  
  
  CONCLUSIONS
  General anesthesia eliminates recall of intraoperative events, including pain. Using an animal model, we refuted the hypothesis that lack of recall results from the analgesia (i.e., the reduced response to painful stimuli produced by inhaled drugs) rather than from a direct effect on learning.
authors.affiliation: Department of Anesthesia, University of California-San Francisco 94143-0464, USA. jim_sonner@quickmail.ucsf.edu
authors.forename: J M
authors.initials: JM
authors.lastname: Sonner
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: E I
authors.initials: EI
authors.lastname: Eger
mesh_terms: D000280:Administration, Inhalation; D000777:Anesthetics / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D017402:Chlorofluorocarbons / Q000494:pharmacology*; D003214:Conditioning, Classical / Q000187:drug effects*; D003503:Cyclobutanes / Q000494:pharmacology*; D000077335:Desflurane; D004305:Dose-Response Relationship, Drug; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology; D007858:Learning / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects
chemical_list: D000777:Anesthetics; D018685:Anesthetics, Inhalation; D017402:Chlorofluorocarbons; D003503:Cyclobutanes; C090640:1,2-dichloro-1,2,3,3,4,4-hexafluorocyclobutane; D000077335:Desflurane; D007530:Isoflurane