A comparison of cholinesterase inhibitors in the treatment of quinuclidinyl benzilate-induced behavioural deficit in rats performing the multiple T-maze

Abstract

Cholinesterase inhibitors are beneficial in the treatment of Alzheimer's disease via indirect increase of cholinergic neuro-transmission. The aim of the present study was to evaluate the potency of inhibitors tacrine, rivastigmine and donepezil to reverse cholinergic depletion induced by 3-quinuclidinyl benzilate (QNB, 2mgkg−1) in Wistar rats performing the multiple T-maze test. The effect of QNB on retention was compared to the effect of standard amnesic drug, scopolamine, at the dose of 0.3mgkg−1. Well-trained rats were treated intra-peritoneally with QNB, followed by another injection containing saline or tacrine (10mgkg−1) or rivastigmine (1.2mgkg−1) or donepezil (2.65mgkg−1) 15min later. Rats were subjected to the T-maze task 30min and 24h following QNB administration. The passage time and number of errors were observed. QNB significantly impaired the performance of rats in both tested times in contrast to short-lasting effect of scopolamine (30min only). The inhibitors rivastigmine and donepezil significantly attenuated QNB-induced behavioural impairment in the 30min tests, whereas tacrine failed to have the same effect. Moreover, the performance of tacrine-treated rats was worse due to cholinergic over-stimulation. Beneficial effects of all tested inhibitors including tacrine were evident in the 24h test.