Cholinesterase inhibitors, donepezil and rivastigmine, attenuate spatial memory and cognitive flexibility impairment induced by acute ethanol in the Barnes maze task in rats

Abstract

Central cholinergic dysfunction contributes to acute spatial memory deficits produced by ethanol administration. Donepezil and rivastigmine elevate acetylcholine levels in the synaptic cleft through the inhibition of cholinesterases—enzymes involved in acetylcholine degradation. The aim of our study was to reveal whether donepezil (acetylcholinesterase inhibitor) and rivastigmine (also butyrylcholinesterase inhibitor) attenuate spatial memory impairment as induced by acute ethanol administration in the Barnes maze task (primary latency and number of errors in finding the escape box) in rats. Additionally, we compared the influence of these drugs on ethanol-disturbed memory. In the first experiment, the dose of ethanol (1.75 g/kg, i.p.) was selected that impaired spatial memory, but did not induce motor impairment. Next, we studied the influence of donepezil (1 and 3 mg/kg, i.p.), as well as rivastigmine (0.5 and 1 mg/kg, i.p.), given either before the probe trial or the reversal learning on ethanol-induced memory impairment. Our study demonstrated that these drugs, when given before the probe trial, were equally effective in attenuating ethanol-induced impairment in both test situations, whereas rivastigmine, at both doses (0.5 and 1 mg/kg, i.p.), and donepezil only at a higher dose (3 mg/kg, i.p.) given prior the reversal learning, attenuated the ethanol-induced impairment in cognitive flexibility. Thus, rivastigmine appears to exert more beneficial effect than donepezil in reversing ethanol-induced cognitive impairments—probably due to its wider spectrum of activity. In conclusion, the ethanol-induced spatial memory impairment may be attenuated by pharmacological manipulation of central cholinergic neurotransmission.

Assessment of spatial learning and memory in the Barnes maze task in rodents—methodological consideration

“…To our knowledge, there is no paper in literature, either for rats or mice, regarding if and/or how the number of holes on platform circumference may affect their performance in the BM task. Nevertheless, in utilizing rats as the study species, the characteristics of the circular platform are usually as follows: 100–122 cm in diameter, with 18–20 circular holes, elevated 80–90 cm above the floor (Gawel et al 2016; Greferath et al 2000; Morel et al 2015). Less frequently for rats, the number of holes around the circumference is 12 (Locklear and Kritzer, 2014; McLay et al 1999).…”

“…Eventually, in the next set of experiments, we decided to decrease the number of trials to two/day but extend it 1 day (5 days, in total 10 trials). Thus, it seems that the number of cues within the surroundings of the maze affected the performance of rats in the BM task (Gawel et al 2016; Marszalek-Grabska et al 2018). …”

“…Although there are in the literature different approaches to adding buzzers as aversive stimuli, in most, a buzzer is switched on immediately when the start tube is raised and is not switched off until the mouse enters the escape hole (Bach et al 1995; Gawel et al 2016; Greferath et al 2000; O’Leary and Brown 2012; Sunyer et al 2007). While most authors used only bright light or a combination of bright light and buzzer as a negative stimuli, Inman-Wood et al (2000) employed bright light, buzzer, and fan.…”

“…Despite the number of different available measuring devices, data may be collected by a highly trained observer with the use of manual stopwatches to record the latency to find the goal box, the number of errors committed by each animal, as well as the strategy used to resolve the maze (Harrison et al 2006; Gawel et al 2016). However, we strongly recommend prior to the BM task to test locomotor activity or motor coordination of animals (e.g., after the injection of tested compound) to assess whether potential disturbances are in fact memory impairments but not decreased locomotor activity.…”

“…This is done 24 h before the first acquisition trial. We believe that this type of habituation, preceded by the handling of the animals for few days prior the BM task, is enough for the rats to familiarize themselves with both the maze surface and escape box, as well as to reduce their anxiety (Gawel et al 2016; Marszalek-Grabska et al 2018). In the Sunyer et al (2007) work (the most frequently adopted procedure for the BM task in mice), the authors recommend one session (the shaping trial) in which they placed the mouse in the center of the maze and covered it by the chamber, lifting this 10 s later.…”