Effect of 5-hydroxytryptophan acting from the cerebral ventricles on 5-hydroxytryptamine output and body temperature.

1. In cats anaesthetized with intraperitoneal pentobarbitone sodium the third ventricle, the anterior or inferior horn of the left lateral ventricle, was perfused with 5-hydroxytryptophan (5-HTP) in different concentrations, and the effluent assayed for 5-hydroxytryptamine (5-HT) on the rat stomach strip preparation of Vane (1957).2. On perfusion of the third ventricle with 5-HTP the output of 5-HT in effluent increased, the increase depending on the 5-HTP concentration: with 1/50,000 it increased 44-69 times (mean 55), with 1/25,000, 81-83 times (mean 82) and with 1/10,000, 71-200 times (mean 128). The 5-HT output depended also on the initial output during the preceding perfusion with artificial c.s.f. The greater this initial output the greater was the maximum output reached during the 5-HTP perfusion.3. The increase in 5-HT output during perfusion of the third ventricle with 5-HTP was usually associated with shivering and a rise in rectal temperature. This association, however, was not invariably obtained, probably because of a central depressant effect of 5-HTP itself.4. On perfusion of the anterior or inferior horn of the left lateral ventricle with 5-HTP, the output of 5-HT in the effluent also increased, but to a lesser extent than in the effluent from the third ventricle. There was no association with shivering nor with a rise in rectal temperature.5. An injection of 1 or 2 mg 5-HTP into the cerebral ventricles of unanaesthetized cats produced a biphasic rise in temperature, shivering, constriction of the skin vessels followed by vasodilatation, tachypnoea, wiping and scratching movements, miaowing and long lasting sleep.6. The biphasic rise in temperature is explained as the result of two opposing effects: increased formation of 5-HT which would raise body temperature, and a central depressant effect of 5-HTP itself or of one of its metabolites which would lower body temperature.7. The initial rise in temperature and the shivering in response to an intraventricular injection of 5-HTP varied from cat to cat. In those in which these effects were strong the 5-HT output during a subsequent perfusion of the third ventricle with artificial c.s.f. was higher, and the maximum 5-HT output reached on perfusion with 5-HTP was greater than in those in which these effects had been weak.