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

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 5 groups (6 rats each): (I) normal control group, (II) untreated diabetic group, and Groups (III-V) diabetic rats received donepezil at a dose of 4 mg/kg orally for twenty days after the first 30 days of diabetes. Group 4 also received 20 mg/kg i.p., L-NAME simultaneously with donepezil for the last 20 days, while group 5 received 40 mg/kg i.p., L-Arginine during this period. A single dose of streptozotocin was used to induce experimental type 1 diabetes. 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.