OPPOSITE EFFECTS OF GABA(A) AND NMDA RECEPTOR ANTAGONISTS ON ETHANOL-INDUCED BEHAVIORAL SLEEP IN RATS

The effects of the GABA(A) receptor antagonists, pentylenetetrazol, bi cuculline, and picrotoxin, the glycine antagonist, strychnine, and the NMDA receptor antagonist, memantine, on ethanol-induced behavioral sl eep and body temperature were investigated. Pentylenetetrazol, bicucul line, and picrotoxin given prior and following ethanol reduced the beh avioral sleep and potentiated the hypothermia caused by ethanol. Howev er, convulsions appeared when bicuculline, but not pentylenetetrazol a nd picrotoxin, were given following ethanol. After the reversal of unc onsciousness in rats without convulsions the animals remained awake th roughout the experiments without motor incoordination, hyperexcitabili ty, and sedation, but they were in hypothermia within 12 h. The glycin e antagonist, strychnine, given prior or after ethanol had virtually n o effect on ethanol-induced behavioral sleep and hypothermia. Ethanol given prior or following strychnine failed to antagonize strychnine in duced convulsions. The NMDA receptor antagonist, memantine, given foll owing ethanol potentiated the behavioral sleep and had virtually no ef fect on hypothermia induced by ethanol. It is suggested that the ethan ol-induced behavioral sleep may be attributed to its ability to enhanc e the GABAergic mechanisms and to inhibit NMDA-mediated excitatory res ponses. However, the ethanol-induced hypothermia may be ascribed solel y to the facilitation of GABAergic transmission. Further, it is postul ated that a bidirectional inhibitory system subserves the regulation o f behavioral sleep and convulsions. However, one-way inhibitory system underlies the ethanol-induced hypothermia. (C) 1997 Elsevier Science Inc.