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Assessing Changes in Volatile General Anesthetic Sensitivity of Mice after Local or Systemic Pharmacological Intervention
Published on: October 16, 2013
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
Abstract:
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.
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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