Anti-depression effects of oxytocin on postpartum depression model rats and its mechanism

Objective To investigate the expression of oxytocin (OXT) and oxytocin receptor (OXTR) in the prefrontal cortex of postpartum depression (PPD) rats induced by restraint stress during pregnancy and to observe the antidepressant effect of oxytocin and its analogue capitoxin and its mechanism. Methods Twenty-four adult female SD rats of SPF grade were randomly divided into control group, PPD + saline group, PPD + oxytocin group and PPD + captopril group with 6 rats in each group. Rats were subjected to restraint stress for 2 hours every day on the 8th to 21st day of pregnancy to establish PPD model.While the rats in control group were not given any treatment.Rats in PPD + saline, PPD + oxytocin and PPD + captopril were injected bilaterally into prefrontal cortex (PFC) at 10 days postpartum (1 μl/side), oxytocin (30 ng/side) and captopril (45 ng/side) respectively once a day for 5 days. The depressive behaviors of rats were detected by sugar-water preference experiment. Rats were sacrificed 18 days after delivery. The expression of OXT was detected by ELISA method, OXTR by Western blot, Iba-1 by immunofluorescence, and IL-1β, IL-6 and TNF-α by qRT-PCR. Results (1) The sucrose consumption of the PPD + saline group ((67.1±10.4)%) was significantly lower than that of the control group((92.6±3.9)%, t=-5.31, P<0.01). (2) The expression of oxytocin in prefrontal cortex in PPD group was significantly lower than that in control group ((0.03±0.01) ng/mg) vs (0.08 + 0.05) ng/mg, t=-2.67, P<0.05). However, there was no significant difference in the expression of oxytocin receptor between PPD group and control group ((0.90±0.06) vs (0.90±0.05), t=0.709, P=0.517). (3) The sucrose consumption of PPD+ saline group decreased than that of control group((65.6±16.9)% vs (91.5±3.5)%, t=3.35, P<0.001). Compared with PPD+ saline group, the sucrose consumption of PPD+ oxytocin group ((81.8±8.4)%) and PPD+ carbetocin group ((78.4±9.4)%) increased(t=1.98, 1.68, both P<0.05). (4) The expression of Iba-1 in the prefrontal lobe of PPD + saline group was higher than that of control group ((1.15±0.05) vs (1.04 + 0.06), t=3.50, P<0.01). Compared with PPD + saline group, the expression of Iba-1 in PPD + oxytocin group (1.03±0.06) and in PPD + captopril group (1.00±0.02) were lower (t=-3.50, -6.55, both P<0.01). (5) The expression of inflammatory factors IL-1β mRNA (1.0±0.1), IL-6 mRNA (1.1±0.1) and TNF-α mRNA (1.7±0.4) in the prefrontal cortex of rats in the PPD group were higher than that in the control group (IL-1β mRNA (0.7±0.3), IL-6 mRNA (0.9±0.1), TNF-α mRNA (1.1±0.3), t=1.92, 3.19, 2.43 respectively, all P<0.05). The expression of inflammatory factors IL-1β, IL-6 and TNF-α mRNA of the PPD+ oxytocin group(IL-1β mRNA (0.6±0.1), IL-6 mRNA (0.9±0.1), TNF-α mRNA (1.2±0.4) )and the PPD+ carbetocin group (IL-1β mRNA (0.7±0.1), IL-6 mRNA (0.9±0.1), TNF-α mRNA (1.0±0.2))in the prefrontal cortex were lower than that in the PPD group(t=-3.17, -2.78, -1.84, t=-2.76, -2.40, -2.94 respectively, all P<0.05). Conclusion Oxytocin and capitoxin injected into prefrontal cortex can effectively improve depression-like behaviors in PPD model rats. Activation of microglia and decrease of inflammatory factors in prefrontal cortex may be the potential antidepressant mechanism. Key words: Postpartum depression; Prefrontal cortex; Oxytocin; Oxytocin receptor; Carbetocin; Inflammatory factors; Rat