J Appl Biomed 12:211-217, 2014 | DOI: 10.1016/j.jab.2014.01.006

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

Jan Misik^*, Jiri Kassa

University of Defence, Faculty of Military Health Sciences, Department of Toxicology, Třebešská 1575, 500 01 Hradec Králové, Czech Republic

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, 2 mg kg^-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 0.3 mg kg^-1. Well-trained rats were treated intra-peritoneally with QNB, followed by another injection containing saline or tacrine (10 mg kg^-1) or rivastigmine (1.2 mg kg^-1) or donepezil (2.65 mg kg^-1) 15 min later. Rats were subjected to the T-maze task 30 min and 24 h 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 (30 min only). The inhibitors rivastigmine and donepezil significantly attenuated QNB-induced behavioural impairment in the 30 min 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 24 h test.

Keywords: Tacrine; Rivastigmine; Donepezil; Neurotransmission; Alzheimer's disease; Spatial orientation; Acetylcholinesterase; Acetylcholine; Muscarinic receptors; Memory

Received: October 23, 2013; Revised: January 2, 2014; Accepted: January 20, 2014; Published: November 1, 2014  Show citation