The Protective Effects of Nicotine and Bucladesine on Impaired Avoidance Memory Caused by Sodium Arsenate Toxicity in Mice

Background: The toxic effect of sodium arsenate on nervous system has been shown; but the protective effects of several compounds against sodium arsenate are not clear. This study aimed to investigate the protective effects of nicotine and bucladesine, two positive modulators of neuronal function, on sodium arsenate toxicity against avoidance memory impairment. Methods: Male mice (N=154) were assigned to 22 groups (12 experimental and 10 control) of seven animals each and were treated as follows: sodium arsenate (2.5, 5, or 10 mg/kg) for 28 days, nicotine (1mg/kg) for either 1, 2, or 4 days, bucladesine (600 nM/mouse) for either 1, 2, or 4 days, and nicotine (1 mg/kg) + bucladesine (600nM/mouse) + sodium arsenate (2.5 mg/kg). The last group was treated with 2.5 mg/kg sodium arsenate first, and then received the combination of nicotine and bucladesine for 1, 2, or 4-days. The corresponding control groups did not receive any drug but either saline, deionized water, or combination of deionized water and DMSO, but went through the same procedure as other animals. All mice were trained 24 hours in the step-through passive avoidance task. The avoidance memory retention was assessed at 24, 48, 96, and 168 hours after the training period by measuring the time they stayed in a dark chamber. Results: All sodium arsenate doses significantly reduced the time stayed in the dark chamber regardless of the treatment duration (24, 48, 96 & 168 hr) after training. Both nicotine and bucladesine, whether used singly or combined for 1, 2, and 4 days significantly enhanced the time latency compared to the controls at all of the experimental timepoints following the training. Conclusions: Nicotine and bucladesine showed synergistic effects and reversed the sodium arsenate-induced avoidance memory deficits in mice.