By stimulating muscle proteolysis and inhibiting protein synthesis, glucocorticoids play a major role in the induction of muscle atrophy in catabolic conditions. Previously, we demonstrated that muscle IGF-I gene electrotransfer prevents muscle atrophy caused by glucocorticoids. In the present study, we have investigated if overexpression of a constitutively active form of Akt1 (caAkt1), a potential intracellular mediator of anabolic and anticatabolic action of IGF-I, could mimic this IGF-I anti-atrophic effects. Localized overexpression of caAkt1 in tibialis anterior (TA) muscle was performed by injection of DNA followed by electroporation 3 days before starting dexamethasone injections (0.1 mg/kg/d SC). A total of 100 mg of caAkt1 DNA inserted in the plasmid pCMV5 under control of the CMV promoter was injected in 10 injections of 10 mg each, followed by 10 pulses of 200 V/cm applied in 20 ms square wave at 1 Hz. Muscle fibers expressing caAkt1 were identified by the presence of a hemagglutinin tag. A control plasmid was electroporated in the contralateral TA muscle. Ten days after electroporation, animals were sacrificed by decapitation and TA muscles were collected. As expected, dexamethasone induced muscle atrophy. Indeed, fiber cross-sectional area (1446±33 vs. 1674±59 mm², n=6, P <0.05) was decreased in dexamethasone-treated animals compared to control animals. In contrast, fibers overexpressing caAkt1 are much larger in size compared with untransfected muscle fibers in both control (4813±224 vs. 1674±59 mm², n=6, P <0.001) and dexamethasone-treated (3846±210 vs. 1446±33 mm², n=6, P <0.001) animals. In conclusion, this work demonstrates that Akt1 gene electrotransfer prevents muscle atrophy induced by glucocorticoids. In further investigations, we plan to test downstream intracellular mediators involved in IGF-I anticatabolic action.