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Introduction:Previous studies have shown that the cannabinoid system is involved in anxiety. In addition, transient receptor potential vanilloid type-1 (TRPV1) channels are new targets for the development of anxiolytics. The present study investigated the possible interaction between the cannabinoid and vanilloid systems on anxiety-like behavior in rats.Methods:Four different groups of male Wistar rats received intraperitoneal (IP) injections of (1) vehicle (DMSO+saline), (2) cannabinoid receptor agonist WIN55212-2 (WIN) (1 mg/kg), (3) TRPV1 receptor antagonist capsazepine (CPZ) (5 mg/kg), or (4) combined WIN (1 mg/kg) and CPZ (5 mg/kg) treatment 30 minutes before testing in the elevated plus maze.Results:The results showed that compared to the control (vehicle), both WIN and CPZ increased the time spent and number of entries on the open arms. Co-administration of WIN and CPZ had a synergistic effect, i.e., the number of entries and time spent on the open arms was greater than that in the groups administered the two compounds alone. The total distance travelled by rats and total number of entries on to the arms did not significantly differ between groups.Conclusion:Acute neuropharmacological blockade of the TRPV1 receptor or stimulation of the CB1 receptor produced an anxiolytic effect. It seems that antagonism of the vanilloid system modulates cannabinoid gain that rises the anxiolytic effect. TRPV1 antagonism may amend generation of endocannabinoids, which in turn increases anxiolytic impact. These results suggest that two systems could act on or share a common signaling pathway affecting the expression of anxiety.