Abstract
ObjectiveAnxiety behavior is regulated by different neurotransmitter systems. There has been no direct relationship between endocannabinoid and cholinergic systems on anxiety in previous studies. This study investigated the effects of each of these systems separately and simultaneously using Donepezil (Cholinesterase inhibitor) and URB-597 (endocannabinoid degrading enzyme inhibitor) on anxiety-like behavior. MethodEighty-eight male mice were divided into eleven groups (n=8) including control (saline), diazepam (0.3 mg /kg), URB-597 (0.1, 0.3, or 1 mg /kg), donepezil (0.5, 1 or 2 mg/kg) and the combination of the two drugs at low, medium and high doses. All treatments were injected intraperitoneally 30 minutes before the elevated plus maze test. ResultsSeparate administration of URB597, donepezil or diazepam increased the number and time spent of open arms compared to the control group. Concurrent administration of URB and donepezil at low, medium and high doses did not change the number of open arms entries compared to the control group, but they reduced the number of entries to the closed arms. ConclusionsThese results suggest that strengthening any cholinergic or endocannabinoid system has anxiolytic effect similar to diazepam. However, the interaction of these two systems has fewer anxiolytic effects compared to the effects of each alone. It seems that these drugs alone may represent a strategy for the treatment of anxiety disorders.
Cholinergic systems are essential for late-stage maturation and refinement of motor cortical circuits
