Effects of intracerebroventricular administration of pituitary adenylate cyclase-activating polypeptide (PACAP) on the motor activity and reserpine-induced hypothermia in murines

We investigated the effects of i.c.v. administration of pituitary adenylate cyclase-activating polypeptide (PACAP) on the spontaneous motor activity and reserpine-induced hypothermia in murines. The administration of PACAP (1 or 2 nmol) caused a dose-dependent increase in both spontaneous motor activity and rearing behavior in the rat. The peptide (0.1 or 0.2 nmol) counteracted reserpine-induced hypothermia in a dose-dependent manner in mice. On the other hand, i.c.v. injection of vasoactive intestinal polypeptide, which is structurally similar to PACAP, at a dose similar to that of PACAP (2 nmol in rats, 0.2 nmol in mice) did not show a significant effect on either behavior or body temperature. Therefore, the stimulating effect of PACAP observed here may be mediated by PACAP-specific (type I) receptors. PACAP was more potent and longer-lasting than a known potent stimulating peptide, thyrotropin-releasing hormone, in both stimulating motor activity and counteracting reserpine-induced hypothermia. Results of the present study, in combination with those of previous studies identifying endogenous PACAP in the brain, suggest that PACAP may play an important role in the CNS as a stimulant in regulating motor activity and body temperature.