NMDA enhances the central depressant properties of ethanol in mice.
Male Swiss-Webster mice were used to examine the effect of NMDA on the ethanol-induced loss of the righting reflex (LORR). The LORR was used as a measure of CNS depression. Immediately after animals regained the righting reflex following ethanol injection (4.0 g/kg, IP) mice received an ICV injection of saline or NMDA (10, 50, 100, or 500 nmol/kg) in a volume of 5 microliters. Upon ICV injection of NMDA, mice again lost the righting reflex and this effect of NMDA in the presence of ethanol occurred rapidly and in a dose-dependent manner. In another experiment DL-2-amino-5-phosphonovaleric acid (APV), a competitive antagonist of NMDA, was given ICV with NMDA (50 nmol/kg) in the presence of ethanol. APV (10 and 100 nmol/kg, ICV) significantly attenuated the response of NMDA to enhance the depressant action of ethanol. When bicuculline methiodide, an antagonist of GABA, was given ICV with NMDA (50 nmol/kg), bicuculline methiodide reduced the effect of NMDA to produce a second loss of the righting reflex (return to the LORR) in the presence of ethanol. When NMDA (100 nmol/kg, ICV) was injected in the absence of ethanol into mice, NMDA by itself did not produce a loss of the righting reflex. In this investigation, the results suggest that NMDA can augment ethanol-induced depression possibly through an interaction between glutamatergic and GABAergeric systems in the CNS.
Department of Pharmacology, Hahnemann University, School of Medicine, Philadelphia, PA 19102.
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D018756:GABA Antagonists; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects
D002492:Central Nervous System Depressants; D018756:GABA Antagonists; D000431:Ethanol; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D001640:Bicuculline