Differential actions of RO 15-1788 and diazepam on poikilothermia, motor impairment and sleep produced by ethanol.
In adult male Sprague-Dawley rats kept at an ambient temperature of 23-25 degrees C, ethanol was injected intraperitoneally in a dose of 4.0 g/kg to produce a clear-cut impairment of autonomic and motorial functions. Following the injection of ethanol, motor coordination, measured on a rotorod, behavioral sleep, righting reflex and colonic temperature were monitored at predetermined intervals for 5.0-7.0 hr. In the first experiment, either 1.0 mg/kg RO 15-1788 (flumazenil), a benzodiazepine (BZ), receptor antagonist, or 1.0-5.0 mg/kg diazepam, a classical benzodiazepine receptor agonist, were injected intraperitoneally either alone or concurrently with ethanol's administration. In the second study, either RO 15-1788 (1.0 or 2.0 mg/kg) or diazepam (1.0 or 5.0 mg/kg) was injected at the nadir of the fall of body temperature induced by ethanol. Although RO 15-1788 alone failed to affect the rats' temperature, it did not prevent the characteristic ethanol-induced hypothermia but rather potentiated it in a dose-dependent manner. Further, this BZ receptor antagonist exacerbated motor incoordination and other behavioral effects when given either simultaneously with ethanol or at the nadir in the animals' core temperature. Although diazepam evoked a dose-dependent hypothermia, it did not enhance ethanol-induced hypothermia when both drugs were administered simultaneously. However, diazepam augmented motor incoordination and other effects and served to delay their recovery. When given to the rats at the nadir of ethanol hypothermia, diazepam did not potentiate ethanol's thermolysis but retarded the recovery from hypothermia; it caused also a dose-dependent delay in the recovery of motor coordination and other responses.(ABSTRACT TRUNCATED AT 250 WORDS)
Paez
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Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27834.
Myers
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D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology*; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005442:Flumazenil / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012890:Sleep / Q000187:drug effects*
D000431:Ethanol; D005442:Flumazenil; D003975:Diazepam