Effects of Xiaoyaosan on Stress-Induced Anxiety-Like Behavior in Rats: Involvement of CRF1 Receptor

Abstract

Background. Compared with antidepressant activity of Xiaoyaosan, the role of Xiaoyaosan in anxiety has been poorly studied. Objective. To observe the effects of Xiaoyaosan on anxiety-like behavior induced by chronic immobilization stress (CIS) and further explore whether these effects were related to CRF1R signaling. Methods. Adult male SD rats were randomly assigned to five groups (n = 12): the nonstressed control group, vehicle-treated (saline, p.o.) group, Xiaoyaosan-treated (3.854 g/kg, p.o.) group, vehicle-treated (surgery) group, and antalarmin-treated (surgery) group. Artificial cerebrospinal fluid (0.5 μL/side) or CRF1R antagonist antalarmin (125 ng/0.5 μL, 0.5 μL/side) was bilaterally administered into the basolateral amygdala in the surgery groups. Except for the nonstressed control group, the other four groups were exposed to CIS (14 days, 3 h/day) 30 minutes after treatment. On days 15 and 16, all animals were subjected to the elevated plus-maze (EPM) and novelty suppressed feeding (NSF) test. We then examined the expression of CRF1R, pCREB, and BDNF in the amygdala. Results. Chronic pretreatment with Xiaoyaosan or antalarmin significantly reversed elevated anxiety-like behavior and the upregulated level of CRF1R and BDNF in the amygdala of stressed rats. pCREB did not differ significantly among the groups. Conclusions. These results suggest that Xiaoyaosan exerts anxiolytic-like effects in behavioral tests and the effects may be related to CRF1R signaling in the amygdala.

Figure 1

Elevated plus maze test. (a) The total distance moved. (b) The percentage of entries in open arms. (c) The percentage of time spent in the open arms. Values are mean ± SEM with 10 rats in each group. ^∗∗ p < 0.01 versus the nonstressed control group. ^# p < 0.05 versus the vehicle-treated CIS group. ^$ p < 0.05 versus the vehicle-treated CIS group after surgery.

Figure 2

Novelty suppress feeding test. (a) Latency to begin eating. (b) Food consumption. (c) Percent loss of body weight. Values are mean ± SEM with 10 rats in each group. ^∗∗ p < 0.01 versus the nonstressed control group. ^# p < 0.05 versus the vehicle-treated CIS group. ^$ p < 0.05 versus the vehicle-treated CIS group after surgery.

Figure 3

Expression of CRF1R, BDNF, and pCREB. (a) Expression of CRF1R in the amygdala. (b) Expression of BDNF in the amygdala. (c) Expression of pCREB in the amygdala. Values are mean ± SEM with 6 rats in each group. ^∗ p < 0.05 and ^∗∗ p < 0.01 versus the nonstressed control group. ^# p < 0.05 versus the vehicle-treated CIS group. ^$ p < 0.05 versus the vehicle-treated CIS group after surgery.