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 n 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 a important role in the CNS as a stimulant in regulating motor activity and body temperature.
Masuo
Y
Y
Discovery Research Laboratories I, Takeda Chemical Industries, Ibaraki,Japan.
Noguchi
J
J
Morita
S
S
Matsumoto
Y
Y
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects*; D009479:Neuropeptides / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000037:antagonists & inhibitors*; D013268:Stimulation, Chemical; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
C495402:Adcyap1 protein, mouse; C495403:Adcyap1 protein, rat; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide; D013973:Thyrotropin-Releasing Hormone; D012110:Reserpine