- Intrathecal (i.t.) administration of substance P in the awake rat decreases reaction time (RT) in the tail flick test. In the anaesthetized rat, noxious thermal stimulation of the tail (by immersion of tip in water at 55 degrees C) also decreases RT; this effect is blocked by a substance P antagonist. The present study examines the effects of calcitonin gene-related peptide (CGRP) on the decrease in RT produced in these two paradigms. Pretreatment with CGRP (3.25 nmol, i.t.) attenuated and abolished the decreases in RT produced by substance P (3.25 nmol, i.t.) and by noxious cutaneous stimulation, respectively. These results indicate an interaction of CGRP and substance P in the regulation of the tail flick reflex.