Effects of cholecystokinin octapeptide on thermoregulatory responses and hypothalamic neuronal activity in the rat

Rats were chronically implanted with a hypothalamic cannula to allow chemical stimulation of the hypothalamus on the conscious animals in repeated experiments. Direct administration of cholecystokinin octapeptide (CCK-8) (20-60 ng) into the preoptic anterior hypothalamic area caused a dose-related fall in rectal temperature at ambient temperatures of 8 degrees C and 22 degrees C. The hypothermia induced by CCK-8 was produced by a decrease in metabolism at an ambient temperature of 8 degrees C, whereas at 22 degrees C, it was caused by both a decrease in metabolism and an increase in cutaneous temperature. However, at an ambient temperature of 30 degrees C, intrahypothalamic administration of CCK-8 caused an insignificant change in thermoregulatory responses. Furthermore, neither intrahypothalamic injection of 0.9% saline nor intraperitoneal injection of CCK-8 (60 ng) had any effect on thermoregulatory responses at the ambient temperatures of 8 degrees-30 degrees C studied. Under urethane anaesthesia, 59 single neurons in the preoptic anterior hypothalamic area were examined in 29 rats. Each animal was subjected to scrotal warming or cooling and to the administration of CCK-8. Microiontophoretic application of CCK-8 resulted in inhibition of the majority (75%) of cold-responsive neurons as well as excitation of the majority (77.8%) of warm-responsive neurons recorded in the preoptic anterior hypothalamic area. However, the majority (69%) of thermally unresponsive cells were not affected by CCK-8 application. The data indicate that CCK-8, when administered intrahypothalamically, excites warm-responsive neurons and inhibits cold-responsive neurons within the preoptic anterior hypothalamic area to induce hypothermia by promoting an increase in heat loss and a decrease in heat production.