Biphasic changes in body temperature produced by intracerebroventricular injections of histamine in the cat.

1. Intracerebroventricular administration of histamine to cats caused hypothermia followed by a rise in body temperature. 2‐Methylhistamine caused a similar biphasic response, while 3‐methylhistamine had no effect on body temperature and 4‐methylhistamine produced a delayed hyperthermia. Some tolerance to the hypothermic activity developed when a series of closely spaced injections of histamine was given. 2. Doses of histamine and 2‐methylhistamine which altered body temperature when given centrally were ineffective when infused or injected I.V. 3. Pyrilamine, an H1‐receptor antagonist, prevented the hypothermic response to histamine. 4. Hypothermic responses to histamine at an environmental temperature of 22 degrees C were comparable to responses in a cold room at 4 degrees C in both resting animals and animals acting to depress a lever to escape an external heat load. A change in error signal from the thermostat could account for these results. However, lesser degrees of hypothermia developed when histamine was given to animals in a hot environment. In some, but not all animals, this smaller response could be attributed to inadequate heat loss in spite of maximal activation of heat‐loss mechanisms. 5. The hyperthermic response to histamine was antagonized by central, but not peripheral, injection of metiamide, an H2‐receptor antagonist. 6. The results indicate that histamine and related agents can act centrally to cause both hypothermia, mediated by H1‐receptors, and hyperthermia, mediated by H2‐receptors.