Pituitary adenylate cyclase-activating polypeptide hormone (PACAP) at verylow dosages improves memory in the rat

To ascertain whether very low dosages of pituitary adenylate cyclase-activa ting polypeptide (PACAP) influence learning in mammals, immediately after t he acquisition trial of a passive avoidance response (PAR) paradigm, PACAP- 38 was administered intracerebroventricularly at increasing dosages (0, 0.0 2, 0.2, 2, 20, and 200 ng in 10 mul saline) to different groups of rats. Th e mnemonic effects were measured by means of retention testing 48 and 96 h later. At intermediate PACAP-38 concentrations there was a significant mnem onic improvement of the PAR. The maximal effect was observed after the 0.2- ng PACAP-38 administration (longer step-through latencies). There was a les ser effect at the subsequent higher concentration, 2 ng. Higher dosages had no effects. It is concluded that PACAP-38 acts as an enhancer of mammalian mnemonic processes even at very low dosages. The positive effect follows a n inverted U-shaped dose-response curve. The results may be of interest for the therapy of some neuropathological conditions. (C) 2001 Academic Press.