Cysteine sulfinic acid can enhance the central depressant effect of ethanol in mice.
The interaction between ethanol and cysteine sulfinic acid was examined in male Swiss-Webster mice. The loss of the righting reflex (LORR) was used as a measurement of central nervous system depression. In addition, the interaction between ethanol and cysteic acid, a metabolite of cysteine sulfinic acid, was studied. Immediately after the animals regained the righting reflex following ethanol injection (IP), mice were given an ICV injection of saline, cysteine sulfinic acid (1, 15 or 25 mumol/kg) or cysteic acid (1, 15, or 25 mumol/kg). There occurred a return to the LORR within 30 s after the ICV injection of drugs. The return to the LORR by the administration of the amino acids in the presence of ethanol occurred in a dose-dependent fashion. When cysteine sulfinic acid or cysteic acid (25 mumol/kg, ICV) was injected in the absence of ethanol, no loss of the righting reflex occurred. In other experiments, bicuculline methiodide was given ICV with cysteine sulfinic acid (25 mumol/kg), cysteic acid (25 mumol/kg), or GABA (25 mumol/kg) in the presence of ethanol. Bicuculline methiodide, a GABA antagonist, reduced the effects of the three amino acids to produce a return to the LORR in the presence of ethanol. These results indicate that cysteine sulfinic acid, an excitatory amino acid, and cysteic acid can enhance the central depressant properties of ethanol. Since bicuculline antagonized the effects of these two amino acids, a GABAergic mechanism may be involved in the interaction between ethanol and cysteine sulfinic acid or cysteic acid.
Hahnemann University, School of Medicine, Department of Pharmacology, Philadelphia, PA 19102.
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D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003544:Cysteic Acid / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003545:Cysteine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D018756:GABA Antagonists; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects
D002492:Central Nervous System Depressants; D018756:GABA Antagonists; D018377:Neurotransmitter Agents; D000431:Ethanol; C017069:bicuculline methiodide; D003544:Cysteic Acid; D003545:Cysteine; C013461:cysteine sulfinic acid; D001640:Bicuculline