Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP)

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been conserv ed remarkably during evolution and is widely expressed in the mammalian bra in. In Drosophila, mutation of the PACAP homologue results in behavioral de fects, including impaired olfaction-associated learning and changes in etha nol sensitivity. Here, we report the generation of mice lacking the PACAP g ene (PACAP(-/-)). PACAP(-/-) mice were born in the expected Mendelian ratio s but had a high early-mortality rate. The surviving adult PACAP(-/-) mice displayed remarkable behavioral changes; they exhibited hyperactive and exp losive jumping behaviors in an open field, increased exploratory behavior, and less anxiety in the elevated plus maze, emergence, and novel-object tes ts. Analysis of PACAP(-/-) mice brains revealed that the serotonin metaboli te 5-hydroxyindoleacetic acid was slightly decreased in the cortex and stri atum compared with wild-type mice. The present study provides evidence that PACAP plays a previously uncharacterized role in the regulation of psychom otor behaviors.