2-amino-4-(3-4-(methylenedioxy)benzylamino)-6-(3-methoxyphenyl)pyrimidine and Anxiety--Separation

Depressive disorders are both prevalent and debilitating, and a proportion of patients have treatment resistance to classic antidepressants. Recent evidence has implicated the intracellular WNT signaling pathway as having a key role in the pathogenesis of major depressive disorder. In the present study, we investigated the role of β-catenin and transcription factor-4 (TCF4) in the depression-like and anxiety-like behaviors exhibited by mice exposed to maternal separation, or chronic mild stress. Both rodent models of childhood and adulthood stress showed depression and anxiety-like behaviors. During the last three weeks of medication, we applied AMBMP (2-Amino-4-[3,4- (methylenedioxy)benzylamino]-6-(3-methoxyphenyl)pyrimidine) to the maternal separation and chronic stress model for the first time. The drug alleviated the depression-like index in saccharin preference test (SPT) and forced swim test (FST), and anxiety-like index in open field test (OFT) and elevated-plus maze (EPM), and reversed the disruption of β-catenin and TCF4 in stressed mice by upregulating the WNT pathway specifically. Therefore, the WNT pathway may be involved in the mediation of patient recovery and could be a target for novel antidepressants.

Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Anxiety, Separation; Behavior, Animal; Benzodioxoles; beta Catenin; Brain; Chronic Disease; Depression; Disease Models, Animal; Female; Food Preferences; Locomotion; Male; Maternal Deprivation; Maze Learning; Mice, Inbred C57BL; Pyrimidines; Stress, Psychological; Swimming; Transcription Factor 4; Wnt Signaling Pathway