Sleep inducing effects of propofol microinjection into the medial preoptic area are blocked by flumazenil.
The intravenous anesthetic, propofol, has been shown to increase sleep when microinjected into the medial preoptic area (MPA) of the rat. Similar increases in sleep have also been observed with triazolam, pentobarbital and ethanol microinjection. Together, these findings implicate the MPA as an important anatomic site mediating the effects of sedatives on naturally occurring sleep. Although the molecular mechanism by which propofol in the MPA acts to induce sleep is unclear, potentiating effects on the GABA(A) receptor complex may play a role. To assess this possibility, we microinjected propofol alone, and in combination with the benzodiazepine receptor antagonist flumazenil, into the MPA. At a dose of 0.76 microg, flumazenil had no effect on sleep when given alone, and completely blocked the increase in sleep caused by a 40-ng dose of propofol although it did not affect the increase in sleep caused by an 80-ng dose of propofol. These data suggest that the sleep inducing property of propofol is in part mediated by direct or indirect actions on the GABA(A)-benzodiazepine receptor complex.
Tung
A
A
Department of Anesthesia and Critical Care, The University of Chicago, 5841 S. Maryland Ave., MC 4028, Chicago, IL 60637, USA. atung@airway.uchicago.edu
Bluhm
B
B
Mendelson
W B
WB
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology*; D005442:Flumazenil / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011301:Preoptic Area / Q000187:drug effects* / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology
D018686:Anesthetics, Intravenous; D018757:GABA Modulators; D011963:Receptors, GABA-A; D005442:Flumazenil; D015742:Propofol