Serotonin receptors 2A and 1A modulate anxiety-like behavior in post-traumatic stress disordered mice

5-hydroxytryptamine receptors 2A and 1A (5-HT2A and 5-HT1A receptors) are most closely related to anxiety-like behavior in post-traumatic stress disorder. This study was aimed at determining how 5-HT2A and 5-HT1A receptors mediate stress-induced anxiety-like behavior. C57BL/6 mice were exposed to conditioned fear stress combined with single-prolonged stress and injected with corresponding antagonists of 5-HT2A or 5-HT1A receptors or DMSO. The established mouse model was used in conjunction with open-field test, freezing behavioral test and elevated plus maze test. Protein expression levels of 5-HT2A and 5-HT1A receptors, ERK1 and ERK2, pERK1, pERK2 and c-Myc in mice hippocampus were evaluated by Western blot analysis and immunofluorescence labeling. Relative mRNA expression levels of 5-HT2A and 5-HT1A receptors, ERK1, ERK2 and c-Myc were analyzed with RT-qRCR. 5-HT2A receptor plays a significant role in anxiety-like behavior by inhibiting 5-HT1A receptor expression. Effect of 5-HT2A and 5-HT1A receptors on stress-related anxiety-like behavior was elicited via ERK1 and ERK2 phosphorylation. On the basis of our experimental results, we hypothesize interaction between 5-HT2A and 5-HT1A receptors in mouse hippocampus to mediate anxiety-like behavior via ERK pathway.