Prevention of hyperthermia-induced convulsions in immature rat by MR-2266, a kappa antagonist.
The opioid receptor subtypes involved in hyperthermia-induced convulsions were studied by testing different opioid receptor-selective antagonists in unrestrained 15-day-old rats. Saline-injected animals exposed to an ambient temperature of 40 degrees C showed a gradual increase in body temperature reaching a maximum of 40.4 +/- 0.2 degrees C at 60 min. At this time all rat pups had convulsions and died. Similar results were obtained when the animals were pretreated with beta-funaltrexamine or 1 mg/kg ICI-154129. However, the injection of 10 mg/kg ICI-154129 prevented hyperthermia-induced convulsions (only 20% of the rats showed generalized convulsions at 90 min). Rats treated with the kappa antagonist MR-2266 also showed an increase in rectal temperature. However, none of the animals had convulsions or died. These results suggest that the kappa-opioid receptors are involved in convulsions induced by hyperthermia.
Department of Physiology and Pharmacology, School of Medicine, Murcia, Spain.
M L
ML
Laorden
E
E
Carrillo
M M
MM
Puig
D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology* / Q000627:therapeutic use; D004399:Dynorphins / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D006358:Hot Temperature; D008297:Male; D009292:Narcotic Antagonists; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology; D017473:Receptors, Opioid, kappa; D003294:Seizures, Febrile / Q000378:metabolism / Q000517:prevention & control*
D001575:Benzomorphans; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; C027247:MR 2266; D004399:Dynorphins