Unpredictable chronic mild stress-induced depressive-like behaviors in spontaneously hypertensive rats

Objective: The objective is to explore whether hypertension influences unpredictable chronic mild stress (UCMS)-induced depressive-like behaviors and the potential therapeutic effect of Guan-Xin-Shu-Tong capsules (GXST) in controlling hypertension and depressive-like behaviors. Materials and Methods: Fifteen spontaneously hypertensive rats (SHR) and 15 wistar rats were divided into three groups respectively (n = 5, in each group), including control, UCMS, and UCMS + GXST groups. The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) were recorded at baseline and at the end of the experiment. Rats were subjected to seven kinds of UCMS over 4 weeks. GXST treatments were administrated (2.8 g/kg) by intragastric gavage once a day over 4 consecutive weeks during UCMS treatment. Sucrose-preference and open-field tests were used to detect depressive-like behaviors. Results: SHR exposed to 4-week UCMS treatment had lower HR when compared with control and UCMS + GXST groups (P < 0.05); Wister rats receiving UCMS or UCMS + GXST had lower SBP (P < 0.05), lower DBP (P < 0.05) and lower MAP (P < 0.05) than controls. Compared with the controls, UCMS reduced the sucrose preference of Wistar rats, UCMS and UCMS + GXST decreased both grid-crossings and the number of upright postures measured in Wistar rats (P < 0.05). SHR showed lower sucrose consumption, less sucrose preference, and fewer grid-crossings after UCMS than control SHR. However, the lower incidence of upright postures in SHR was prevented by GXST treatment (P < 0.05). Linear correlation showed that grid-crossings or upright postures were negatively related to the values of SBP, DBP, or MAP, presenting the positive relationship between depressive-like behaviors and SBP, DBP, or MAP reduction in Wistar rats; there was a negative correlation between grid-crossings and DBP responses, and MAP responses in SHR, and a positive correlation between depressive-like behaviors and DBP and MAP response elevation in SHR. Conclusions: UCMS-induced depressive-like behaviors in Wistar and SHR, accompanied by a blood pressure decrease in Wistar rats but not in SHR. While GXST exhibited effective relief of depressive-like behaviors in SHR without influencing their blood pressure.