Disruption of Adenylyl Cyclase Type 5 Induces Anti-Depressive Behavior

TRIFIOLIS TL; GUERS J; BUCHHOLZ B; VATNER D; VATNER SF; GELPI RJ

Chicago

Congreso; Experimental Biology; 2017

FASEB

It isgenerally thought that increases in cyclic AMP signaling will induce depressivebehavior. We examined the extent to which behavior was modified by disruptionof adenylyl cyclase type 5 (AC5), which reduces cyclic AMP levels, and which isprevalent in most organs, including the brain. Accordingly, we assessedbehavior using traditional tests, i.e., locomotor activity using an open field,examining total distance traveled, rest time and vertical activity, which wereall 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 ofthe open field test in comparison to the wild type mice. The average totaldistance 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). Resttime was less in AC5 KO. AC5 KO only rested for (3,884 ± 172 s) while AC5 WTremained inactive for (5,745 ± 86 s; p<0.05). AC5 KO moved vertically moreoften (1008 ± 117 counts) than AC5 WT (125 ± 11 counts; p <0.05). Thesedata, in contrast to most of the literature, indicate that AC5 KO mice, whichhave lower cAMP signaling, actually exhibit increased locomotion and stronglysuggesting an anti-depressive behavior. Translating this concept to the clinicswould be a novel therapeutic approach for patients with depression.