Mild deficits in mice lacking pituitary adenylate cyclase-activating polypeptide receptor type 1 (PAC1) performing on memory tasks

Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor subtype 1 (PAC1) have been suggested to play a role in the modulation of l earning and memory. However, behavioral evidence for altered mnemonic funct ion due to altered PAC1 activity is missing. Therefore the role of PAC1 in learning and memory was studied in mouse mutants lacking this receptor (PAC 1 knock-out mice), tested in water maze two-choice spatial discrimination, one-trial contextual and cued fear conditioning, and multiple-session conte xtual discrimination. Water maze spatial discrimination was unaffected in P AC1 mutants, while a mild deficit was observed in multiple session contextu al discrimination in PAC1 knock-out mice. Furthermore, PAC1 knock-out mice were able to learn the association between context and shock in one-trial c ontextual conditioning, but showed faster return to baseline than wild-type mice. Thus, the effects of PAC1 knock-out on modulating performance in the se tasks were subtle and suggest that PAC1 only plays a limited role in lea rning and memory. (C) 2000 Elsevier Science B.V. All rights reserved.