Effect of Scopolamine and Mecamylamine on Antidepressant Effect of Rivastigmine in a Behavioral Despair Test in Mice

Rivastigmine can decrease the severity of depression in Alzheimer’s disease patients. Apart from the monoamines hypothesis of despair, it is well known that the cholinergic system is also responsible. Thus regarding the antidepressant effect of rivastigmine, the aim was evaluating the influence of scopolamine (muscarinic cholinergic receptors antagonist) and/or mecamylamine (nicotinic cholinergic receptors antagonist) co-administration with rivastigmine on depression outcome. Depression was evaluated by the tail suspension test (TST) in male mice. Immobility time was recorded manually which represents the time that animal stops attempts for escape from the unpleasant situation. Imipramine as the reference antidepressant decreased this time by increasing the hope for escape in the animal. Rivastigmine (0.75 mg/kg,sc), scopolamine and/or mecamylamine (0.5 and 1 mg/kg, ip, respectively) were injected before the TST. Rivastigmine considerably reduced the immobility time compared with the control group which indicated its antidepressant effects. The combination treatment of rivastigmine and scopolamine also reduced the immobility time compared with control. Mecamylamine co-administration with rivastigmine increased the immobility time which indicated that it prevented the antidepressant effects of rivastigmine. Ultimately by using the drugs all together the immobility time notably decreased. Therefore our results proved that nicotine cholinergic receptorstimulation is prominent in the antidepressant effects of rivastigmine. Thus nicotine receptor direct or indirect stimulants could be considered for further researches regarding antidepressants.