A cntral site for the hypothermic effects of (+)-amphetamine sulphate and p-hydroxyamphetamine hydrobromide in mice

1. In unanaesthetized mice, weighing 20-30 g, the effect of (+)-amphetamine sulphate and p-hydroxyamphetamine hydrobromide on rectal temperature was examined. The drugs were injected intraperitoneally or into the cerebral ventricles.2. Amphetamine produced hypothermia when injected intraperitoneally in doses of 1-5 mg/kg and intraventricularly in doses of 0.5 to 25 mug. Injections of larger doses-10 mg/kg intraperitoneally and 400 mug intraventricularly-resulted in hyperthermia followed by hypothermia.3. Hydroxyamphetamine produced hypothermia only when given by the intra-ventricular route; the effect was obtained with 0.5 to 25 mug. An intraventricular injection of 200 mug resulted in hyperthermia followed by hypothermia. When injected intraperitoneally the sole effect on temperature was hyperthermia, and this response was obtained with 5 and 10 mg/kg.4. Hydroxyamphetamine injected intraperitoneally or intraventricularly in doses which produced hyperthermia reduced the noradrenaline but not the dopamine content of the brain. When injected intraventricularly in smaller doses which produced hypothermia no reduction in the noradrenaline content of the brain was obtained.5. The hypothermia is attributed to an action on the anterior hypothalamus, and the possibility is discussed that it is brought about indirectly by the release of noradrenaline. The hyperthermia on the other hand is probably a peripheral effect.