title: Halothane prevents MK-801 neurotoxicity in the rat cingulate cortex.
abstract: Subcutaneous administration of the N-methyl-D-aspartic acid (NMDA) antagonist, MK-801, to adult rats causes a toxic vacuole reaction in neurons of the posterior cingulate cortex which is readily detected in histological sections 4 h following MK-801 administration. Certain drugs that facilitate neurotransmission at gamma-aminobutyric acidA (GABAA) receptors block this neurotoxic action of MK-801. The anesthetic actions of halothane (fluothane) are thought to be due, at least in part, to an interaction with GABAA receptors. In the present study, we investigated the effect of halothane on MK-801 neurotoxicity. When halothane was administered for either 1 or 2 h, then terminated immediately prior to MK-801 treatment, the vacuole reaction detected 4 h later was almost as severe as in controls not exposed to halothane. Administration of halothane for 1 h after MK-801 injection postponed but did not prevent a relatively full vacuole reaction. However, when rats were kept under halothane anesthesia continuously throughout the 4 h period following MK-801 administration, the vacuole reaction was completely prevented. We postulate that halothane blocks MK-801 neurotoxicity by a facilitative action at GABAA receptors. Because halothane's duration of action is fleeting compared to the very long duration of action of MK-801, the efficacy of halothane in blocking MK-801 neurotoxicity varies in direct proportion to the length of time following MK-801 treatment that the rat brain is exposed to halothane.
authors.affiliation: Department of Molecular Medical Science, Tokyo Medical and Dental University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ishimaru
authors.forename: F
authors.initials: F
authors.lastname: Fukamauchi
authors.forename: J W
authors.initials: JW
authors.lastname: Olney
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005260:Female; D006179:Gyrus Cinguli / Q000187:drug effects*; D006221:Halothane / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016291:Dizocilpine Maleate; D006221:Halothane