Anxiolytic-like effects of compound zhi zhu xiang in rats

Abstract

The purpose of this study was to determine whether compound zhi zhu xiang (CZZX) exerts anxiolytic-like effects in rats. The animals were orally administered CZZX (0.75, 1.5, and 3 g/kg daily) for 10 days and tested in the elevated plus maze (EPM), Vogel conflict test (VCT), and open field. Repeated treatment with CZZX (3 g/kg/day, p.o.) significantly increased the percentage of both entries into and time spent on the open arms of the EPM compared with saline controls. In the VCT, repeated treatment with CZZX (1.5 and 3 g/kg/day, p.o.) significantly increased the number of punished licks. The drug did not change the total entries into the open arms of the EPM or interfere with water consumption or nociceptive threshold, discarding potential confounding factors in the two tests. In the open field, locomotion was not reduced, discarding the possible sedative effect of CZZX. In the binding assay, the binding of [(3)H] Ro 15-1788 (flumazenil) to the benzodiazepine binding site in washed crude synaptosomal membranes from rat cerebral cortex was affected by CZZX. These data indicate an anxiolytic-like profile of action for CZZX without sedative side effects, and this activity may be mediated by benzodiazepine binding site modulation at γ-aminobutyric acid-A receptors.

Figure 1

Behavioural performance of rat registered in a 5 min session in the elevated plus maze performed 1 h after the injection of vehicle (VEH, p.o.) and CZZX (0.75, 1.5 and 3 g/kg, p.o.) or 0.5 h after the injection of diazepam (DZP, 1 mg/kg, p.o.). (a) Percentage of the number of entries into the open arm, (b) percentage of time spent into the open arms and (c) total arm entries. Columns represent the means ± SEM, n = 9-10 rats. *P < 0.05, **P < 0.01 compared to the control group.

Figure 2

Nubmer of punished licks registered in a 5 min session in the vogel conflict test performed 1 h after the injection of vehicle (VEH, p.o.) and CZZX (0.75, 1.5 and 3 g/kg, p.o.) or 0.5 h after the injection of diazepam (DZP, 1 mg/kg, p.o.). Columns represent the means ± SEM, n = 9-10 rats. *P < 0.05 compared to the control group.

Figure 3

Effects of CZZX on the number of unpunished licks of rats that had been water-deprived for 48 h. Columns represent the means ± SEM, n = 10 rats.

Figure 4

Effects of CZZX on the nociceptive thermal thresholds. Columns represent the means ± SEM, n = 10 rats. ***P < 0.01 compared to the control group.

Figure 5

Effect of CZZX on the exploratory behavior of rats in the open field test. Columns represent the means ± SEM, n = 10 rats. *P < 0.05 compared to the control group.

Figure 6

Activity of CZZX in the [³H] Ro 15-1788 (flumazenil) binding assay. Data represent mean ± SEM of four independent experiments each performed in triplicate.