Abstract: Objective To explore the mechanism of paeoniflorin in improving depression and anxiety of rats through L-type calcium channel. Methods Forty-eight rats were divided into a normal group, a Bayk8644 (L-type Ca²⁺ channel agonist) group, and high dose (200 mg·kg^-1·d^-1), middle dose (100 mg·kg^-1·d^-1) and low dose (50 mg·kg^-1·d^-1) paeoniflorin groups, and a positive control nimodipine group (1 mg·kg^-1·d^-1). The normal group and the Bayk8644 group were given normal saline, and the other groups were given corresponding drugs. After 7 days of continuous administration, Bayk8644 (0.2 mg·kg^-1·d^-1) was injected intraperitoneally into all the groups except the normal group. The open field test (OFT) and elevated plus maze test (EPM) were used to test the depression and anxiety behavior of rats. The expression levels of calmodulin-dependent proteins kinase type Ⅱ (CaMK Ⅱ), brain-derived neurotrophic factor (BDNF) and phosphorylated CaMK Ⅱ (pho-CaMK Ⅱ) in each group were detected by Western blotting. Results Compared with the normal group, the total distance, the time spent in the central area, the distance in the central area, the number of vertical movement, the percentage of open arm time (OT%) and the percentage of open arm entry (OE%) of the Bayk8644 group increased significantly (P<0.05 or P<0.01), the expression levels of CaMKⅡ and pho-CaMK Ⅱ increased significantly (P<0.05 or P<0.01), and the expression level of BDNF decreased significantly (P<0.05). Compared with the Bayk8644 group, the total distance in the central area of the high dose paeoniflorin group increased significantly (P<0.05), the time spent in the central area of the middle and high dose paeoniflorin groups were extended (P<0.05), the OT% and OE% of the high dose paeoniflorin group and the OT% of the middle dose paeoniflorin group decreased significantly (P<0.05 or P<0.01), the expression levels of CaMKⅡ and pho-CaMK Ⅱ proteins in the high dose paeoniflorin groups were significantly reduced (P<0.05 or P<0.01), and the expression level of BDNF protein was significantly increased (P<0.05). Conclusion Bayk8644 can induce depression and anxiety behavior of rats. Paeoniflorin can antagonize the negative effect of Bayk8644 and exert its pharmacological effect by inhibiting the L-type calcium channel and influenceing the activation of CaMKⅡ protein.

Key words: Paeoniflorin, Calcium channel, Bayk8644, Depression, Anxiety, Calmodulin-dependent protein kinase typeⅡ, Rats