Sleep inducing effects of propofol microinjection into the medial preoptic area are blocked by flumazenil

A Tung1, B Bluhm, W B Mendelson

  • 1Department of Anesthesia and Critical Care, The University of Chicago, 5841 S. Maryland Ave., MC 4028, Chicago, IL 60637, USA. atung@airway.uchicago.edu

Brain Research
|July 17, 2001
PubMed

Insights

Propofol increases sleep by acting on the medial preoptic area (MPA). This effect is partly mediated by the GABA(A)-benzodiazepine receptor complex, as shown by flumazenil blocking propofol

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • The medial preoptic area (MPA) is implicated in mediating sedative effects on natural sleep.
  • Propofol, an intravenous anesthetic, increases sleep when microinjected into the rat MPA.
  • Other sedatives like triazolam, pentobarbital, and ethanol also increase sleep via MPA.

Purpose of the Study:

  • To investigate the molecular mechanism of propofol-induced sleep in the MPA.
  • To determine if the GABA(A) receptor complex mediates propofol's sleep-promoting effects.

Main Methods:

  • Microinjection of propofol alone and with flumazenil (a benzodiazepine receptor antagonist) into the rat MPA.
  • Assessment of sleep changes following microinjections.

Main Results:

  • Flumazenil (0.76 microg) alone did not affect sleep.
  • Flumazenil completely blocked the sleep increase from a low dose (40 ng) of propofol.
  • Flumazenil did not block the sleep increase from a higher dose (80 ng) of propofol.

Conclusions:

  • Propofol's sleep-inducing property in the MPA is partly mediated by the GABA(A)-benzodiazepine receptor complex.
  • The interaction with the GABA(A)-benzodiazepine receptor complex may be dose-dependent.

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