Urethane anesthesia reverses the protective effect of noncompetitive NMDA receptor antagonists against cocaine intoxication

The present experiments examined whether pretreatment with the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists, MK-801 and dextrorphan, could antagonize cocaine-induced convulsions and lethality in conscious Sprague-Dawley (SD) rats and whether urethane anesthesia alters the observed interactions. Conscious, restrained male SD rats received continuous i.v. infusions of cocaine hydrochloride (1.25 mg/kg.min) until convulsions and death occurred. Cocaine doses of 21.2±1.8 and 29.5±2.5 mg/kg caused convulsions and death, respectively, in saline treated rats (n = 8). Convulsions were absent in MK-801 (1 mg/kg, i.v.;n = 8) pretreated rats; the lethal cocaine dose was 44.0±2.7 mg/kg (p