The effects of donepezil on anxiety- and depression-like behaviors in diabetic rats and the role of nitric oxide modulators

Aims: The aim of the present study was to evaluate the effect of an acetylcholinesterase inhibitor donepezil on the diabetes-induced anxiety and depression and the role of nitric oxide in these effects. Methods: Thirty male Wistar rats were randomly divided into 2 groups at first; the control group (n=6) and the diabetic group (n=24). The diabetic group divided into four groups, a single dose of streptozotocin was used to induce experimental type 1 diabetes. After 30 days, one group was separated as diabetic control, while the other three received 4 mg/kg p.o. donepezil for 20 days. One of the DON groups was administered 20 mg/kg i.p., L-NAME for 20 days, while the other group was administered 40 mg/kg i.p., L-arginine for 20 days. Results: Anxiety-like behaviors were assessed using the open field test (OFT), and depression-like behaviors were estimated using the forced swim test (FST). In the OFT, all diabetic rats spent less time in the center and engaged in less exploratory behavior than the control group.  The number of lines crossed where locomotor activity was assessed did not differ significantly between groups. In the FST, duration of immobility increased significantly in diabetic groups compared to the control. Donepezil administration did not affect either depression or anxiety responses. Moreover, donepezil plus L-arginine increased diabetes-induced depression significantly. Conclusion: These findings may suggest that cholinergic and nitrergic systems may interact on depression-like behaviors in diabetic rats.