Disruption of Adenylyl Cyclase Type 5 Induces Anti‐Depressive Behavior

It is generally thought that increases in cyclic AMP signaling will induce depressive behavior. We examined the extent to which behavior was modified by disruption of adenylyl cyclase type 5 (AC5), which reduces cyclic AMP levels, and which is prevalent in most organs, including the brain. Accordingly, we assessed behavior using traditional tests, i.e., locomotor activity using an open field, examining total distance traveled, rest time and vertical activity, which were all recorded and analyzed for AC5 knock out (KO) mice and their wild type (WT) littermates. The AC5 KO mice were significantly more active in all aspects of the open field test in comparison to the wild type mice. The average total distance traveled by AC5 KO mice over a two hour testing period was (7,584 ± 749 cm) while WT average total distance was (1,764 ± 99 cm; p<0.05). Rest time was less in AC5 KO. AC5 KO only rested for (3,884 ± 172 s) while AC5 WT remained inactive for (5,745 ± 86 s; p<0.05). AC5 KO moved vertically more often (1008 ± 117 counts) than AC5 WT (125 ± 11 counts; p <0.05). These data, in contrast to most of the literature, indicate that AC5 KO mice, which have lower cAMP signaling, actually exhibit increased locomotion and strongly suggesting an anti‐depressive behavior. Translating this concept to the clinics would be a novel therapeutic approach for patients with depression. Support or Funding Information This study is supported by NIH grant: R01 HL106511.