Interaction between L-glutamate and ethanol on the central depressant properties of ethanol in mice.
The effect of L-glutamate to alter ethanol-induced central depression was studies in male Swiss-Webster mice. The duration loss of the righting reflex (LORR) was used as a measurement of CNS depression. Mice were injected (IP) with ethanol (4.0 g/kg), which caused them to lose the righting reflex. After mice regained the righting reflex following ethanol injection (IP), they were immediately injected (ICV) with saline or L-glutamate (1, 15, or 25 mumol/kg). L-Glutamate induced a return to the LORR within 60 s after ICV injection of drug. When L-glutamate was administered (ICV) in the absence of ethanol, no significant loss of the righting occurred. In other experiments, DL-2-amino-5-phosphonovaleric acid (APV), a competitive inhibitor of NMDA, was given ICV with L-glutamate in the presence of ethanol. APV did not significantly antagonize the interaction between ethanol and L-glutamate. When bicuculline methiodide, a GABA antagonists, was administered with L-glutamate (ICV), bicuculline methiodide reduced the effect of L-glutamate to produce a return to the LORR in the presence of ethanol. These data indicate the L-glutamate, an excitatory amino acid neurotransmitter, can enhance the central depressant action of ethanol. It appears that an interaction between the GABAergic and glutamatergic systems may be involved in ethanol intoxication.
Ferko
A P
AP
Department of Pharmacology, School of Medicine, Hahnemann University, Philadelphia, PA 19102.
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005971:Glutamates / Q000008:administration & dosage / Q000494:pharmacology*; D018698:Glutamic Acid; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D004856:Postural Balance / Q000187:drug effects
D002492:Central Nervous System Depressants; D005971:Glutamates; D000431:Ethanol; D018698:Glutamic Acid; C017069:bicuculline methiodide; D015763:2-Amino-5-phosphonovalerate; D001640:Bicuculline