Opposite effects of GABAA and NMDA receptor antagonists on ethanol-induced behavioral sleep in rats.
The effects of the GABAA receptor antagonists, pentylenetetrazol, bicuculline, and picrotoxin, the glycine antagonist, strychnine, and the NMDA receptor antagonist, memantine, on ethanol-induced behavioral sleep and body temperature were investigated. Pentylenetetrazol, bicuculline, and picrotoxin given prior and following ethanol reduced the behavioral sleep and potentiated the hypothermia caused by ethanol. However, convulsions appeared when bicuculline, but not pentylenetetrazol and picrotoxin, were given following ethanol. After the reversal of unconsciousness in rats without convulsions the animals remained awake throughout the experiments without motor incoordination, hyperexcitability, and sedation, but they were in hypothermia within 12 h. The glycine antagonist, strychnine, given prior or after ethanol had virtually no effect on ethanol-induced behavioral sleep and hypothermia. Ethanol given prior or following strychnine failed to antagonize strychnine-induced convulsions. The NMDA receptor antagonist, memantine, given following ethanol potentiated the behavioral sleep and had virtually no effect on hypothermia induced by ethanol. It is suggested that the ethanol-induced behavioral sleep may be attributed to its ability to enhance the GABAergic mechanisms and to inhibit NMDA-mediated excitatory responses. However, the ethanol-induced hypothermia may be ascribed solely to the facilitation of GABAergic transmission. Further, it is postulated that a bidirectional inhibitory system subserves the regulation of behavioral sleep and convulsions. However, one-way inhibitory system underlies the ethanol-induced hypothermia.
Beleslin
D B
DB
Department of Pharmacology, Medical Faculty, Belgrade, Yugoslavia.
Djokanović
N
N
Jovanović Mićić
D
D
Samardzić
R
R
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology*; D005998:Glycine / Q000037:antagonists & inhibitors; D008297:Male; D008559:Memantine / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000139:chemically induced; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D013331:Strychnine / Q000494:pharmacology
D001640:Bicuculline; D000431:Ethanol; D018756:GABA Antagonists; D005998:Glycine; D008559:Memantine; D010433:Pentylenetetrazole; D010852:Picrotoxin; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D013331:Strychnine