Corticosteroids have been widely used in anti-inflammatory medication. Chronic corticosteroid (CORT) treatment can cause mesocorticolimbic system dysfunctions which is known to play a key role for the development of psychiatric disorders. The ventral tegmental area (VTA) is a critical site in the mesocorticolimbic pathway and is responsible for motivation and reward-seeking behaviors. However, the mechanism by which chronic CORT alters VTA dopamine neuronal activity is largely unknown. We treated peri-adolescent male mice with either vehicle, 1d, or 7d CORT in the drinking water, examined behavioral impacts with light/dark box, elevated plus maze, operant chamber and open field tests, measured the effects of CORT on VTA dopamine neuronal activity using patch clamp electrophysiology and dopamine concentration using fast-scan cyclic voltammetry, and tested the effects of dopamine D2 receptor (D2R) blockade by intra-VTA infusion of a D2R antagonist. CORT treatment induced anxiety-like behavior as well as decr...