Serotonergic Inhibition of Intense Jumping Behavior in Mice Lacking PACAP (Adcyap1

Abstract: Genetic manipulation of pituitary adenylate cyclase-activating polypeptide (PACAP) in mice has uncovered its involvement in psychomotor function. We previously observed that mice lacking the Adcyap1 gene encoding the neuropeptide PACAP (Adcyap1−/−) displayed intense jumping behavior when placed in a novel environment such as an open field. Here, we show that Adcyap1−/− mice manifest jumping behavior as early as at least 6 weeks of age when compared with wild-type mice and that the selective serotonin (5-HT) reuptake inhibitor, fluoxetine, as well as the serotonin precursor, 5-hydroxytryptophan, suppress jumping behavior. Our previous study showed a slight decrease in 5-HT metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in Adcyap1−/− mouse brain. Taken together, these results suggest that there is a developmental aspect to the jumping behavior seen in Adcyap1−/− mice, and that jumping behaviour may involve the serotonergic system.