Study the Effect of Endocannabinoid System on Rat Behavior in Elevated Plus-Maze

Abstract

Introduction: Previous studies have shown that cannabinoidergic system is involved in anxiety. However, there are controversial reports in the experimental studies. The aim of this study is to evaluate the effect of pharmacological stimulation or blocking of CB1 receptors and inhibition of endocannabinoid degradation in anxiety like behavior in elevated plus-maze (EPM) test in rat. The EPM is one of the most widely used animal models of anxiety.

Methods: Male Wistar rats were randomly allocated to ten groups. Different groups of animals intraperitoneally received Win-55212 (0.3, 1 and 5 mg/kg) as CB1 receptor agonist, AM-251 (0.3, 1 and 5 mg/kg) as CB1 receptor antagonist, URB-597 (0.03, 0.1 and 0.3 mg/kg) as endocannabinoid breakdown inhibitor or saline (as control group) 30 min before submitting into EPM test.

Results: The results showed that compared to the control group, Win-55212 (1 and 5 mg/kg) and URB-597 (0.1 and 0.3 mg/kg) significantly increased both of the time and percentage of entries into open arms. AM-251 (1 and 5 mg/kg) significantly decreased the time and percentage of entries into open arms in the EPM test. These substances have no effects on the total distance covered by animals and number of closed arm entries.

Discussion: It is concluded that activation of cannabinoid receptor exert anxiolytic effect while blocking of cannabinoid receptor resulted in anxiety behavior. The locomotor activity was not significantly changed by cannabinoid system. It is suggested that potentiation of cannabinoid system may be therapeutic strategy for the anxiety behavior.

Keywords: Anxiety; Cannabinoids; Rat; URB 597.

Figure 1.

Effect of Win-55212-2 (0.3, 1, and 5 mg/kg) treatment on elevated plus-maze performance: total distance covered by rats (A), the percentage of entries in open arms (B), time spent in open arms (C) and number of closed arms entry (D) during the 10 min test session in EPM. Data were analyzed by one-way ANOVA followed by Tukey–Kramer test (n= 10 per group). ^* P<0.05, and ^** P<0.01 compared to control (saline).

Figure 3.

Effect of URB-597 (0.03, 0.1, and 0.3 mg/kg) treatment on elevated plus-maze performance: total distance covered by rats (A), the percentage of entries in open arms (B), time spent in open arms (C) and number of closed arms entry (D) during the 10 min test session in EPM. Data were analyzed by one-way ANOVA followed by Tukey–Kramer test (n=10 per group). ^* P<0.05, and ^** P< 0.01 compared to control (saline).

Figure 2.

Effect of AM251 (0.3, 1 and 5 mg/kg) administration on the elevated plus-maze performance: total distance covered by rats (A), the percentage of entries in open arms (B), time spent in open arms (C) and number of closed arms entry (D) during the 10 min test session in EPM. Data were analyzed by one-way ANOVA followed by Tukey–Kramer test (n=10 per group). ^* P<0.05, and ^** P<0.01 compared to control (saline).