Time course of the hypothermic response to continuously administered neurotensin

Intracerebroventricular administration of the tridecapeptide neurotensin is known to elicit hypothermia in rodents for few hours. In the present study, we investigated a continuous intracerebroventricular infusion regimen for prolongation of the hypothermic effect. Male Wistar-Han rats (n=13) received neurotensin 10-50 microg/h for 48 h, while their body temperature was monitored continuously. This protocol led to a dose-dependent decrease of body temperature down to 35-36 degrees C. The nadir of hypothermia lasted for approximately 4h and normothermia was re-established after 12-24h. Furthermore, abundance of neurotensin in the hypothalamus was determined after 6 and 30 h by western blotting. High levels were still found at 30 h, while the rats had already become normothermic at that time. In summary, continuous infusion of neurotensin led to prolongation of the known hypothermic response, however resulted in development of tolerance.