Peripheral kappa-opioid agonist, ICI 204448, evokes hypothermia in cold-exposed rats

ICI 204448, a selective kappa-opioid agonist with limited CNS access, can be used to discriminate central and peripheral opioid actions on physiological systems such as pain and thermoregulation. Therefore, we investigated the effect of ICI 204448 (2.5, 5, and 10 mg/kg, s.c.) on male Sprague-Dawley rats exposed to ambient temperatures of 5, 20, or 32 degrees C. ICI 204448 did not alter the body temperature of rats maintained at 20 or 32 degrees C. However, 5 and 10 mg/kg of ICI 204448 evoked significant hypothermia in rats exposed to 5 degrees C. The i.c.v. administration of nor-BNI, a kappa-opioid antagonist, did not affect the hypothermia produced by the systemic injection of ICI 204448. Thus, an involvement of brain kappa-opioid receptors in ICI 204448-evoked hypothermia is unlikely. The present data demonstrate for the first time that ICI 204448 produces hypothermia in cold-exposed rats and suggest that the role of peripheral kappa-opioid receptors in thermoregulation becomes more significant at cold ambient temperatures.