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Clinical reports suggest a potential link between excess retinoids and development of depression. Although it has been shown that all-trans retinoic acid (ATRA) administration induces behavioral changes, further insight into how ATRA is involved is lacking. The hippocampus seems to be a major target of retinoids, and abnormal synaptic plasticity of the hippocampus is involved in depression. We examined two genes associated with synaptic function, discs large homolog 2 (<i>DLG2</i>), and synapse differentiation-inducing gene protein 1 (<i>SynDIG1</i>) in terms of hippocampal expression and correlation with behavior. Three different doses of ATRA were injected into young mice and 10 mg/kg ATRA was found to induce depression-like behavior. In the hippocampus, <i>DLG2</i> mRNA was significantly decreased by ATRA. mRNA levels were positively correlated with central area duration and distance in the open-field test. Increased <i>SynDIG1</i> mRNA levels were observed. There was a negative correlation between <i>SynDIG1</i> mRNA levels and mobility time in the forced swimming test. Retinoic acid receptor γ mRNA was significantly positively correlated with <i>DLG2</i> and negatively correlated with <i>SynDIG1</i>. To summarize, ATRA administration induced anxiety- and depression-like behavior accompanied by a decreased expression of <i>DLG2</i> and an increased expression of <i>SynDIG1</i>. Moreover, <i>DLG2</i> was correlated with anxiety-like behavior and <i>SynDIG1</i> was correlated with depression-like behavior. These results might constitute a novel target underlying ATRA-induced anxiety- and depression-like behavior.