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.