Effects of Cholinesterase Inhibitors Tacrine and Metrifonate on Exploratory Activity in Rats with Induced Hypoxia

Dementia is a common symptom of many degenerative brain diseases. The cholinesterase inhibitors are widely recommended for the treatment of Alzheimer’s disease and different kind of dementia to improve memory functions. Tacrine is the first drug from this group. Metrifonate has been used as an antihelminthic in tropical countries for more than 30 years, and even recently has been suggested as a treatment for dementias. Chronic application of sodium nitrite induced long-lasting effects such as hypoxia, neuron damage and impaired behavior. The aim of our study was to study the effects of Tacrine and Metrifonate on exploratory activity in rats with induced hypoxia. The male Wistar rats (9 per group, with body weight 200220 g) was treated with: 1 st Saline 0.1ml/100g body weight s.c. + Saline 0.1ml/100g body weight p.o. (controls); 2 nd – Sodium nitrite 50 mg/kg s.c. + Saline 0.1ml/100g p.o., 3 rd – Sodium nitrite 50 mg/kg s.c. + Tacrine 0.5 mg/kg p.o.; 4 th – Sodium nitrite 50 mg/kg s.c. + Tacrine 1 mg/kg p.o., 5 th Sodium nitrite 50 mg/kg s.c. + Metrifonate 30 mg/kg p.o., 6 th Sodium nitrite 50 mg/kg s.c. + Metrifonate 50 mg/kg p.o., 7 th Sodium nitrite 50 mg/kg s.c. + Metrifonate 80 mg/kg p.o. The effect of tacrine and metrifonate on exploratory activity of rats was studied in automatic set-up for horizontal and vertical activity “Activity cage” with photo-sensors (Ugo Basile, Italy). Time spent on the apparatus was 5 minutes. The comparison between groups made by Instat computer program using analysis of variance (ANOVA for repeated measurements). In locomotor activity test control rats showed the highest number of relative units compared to all studied groups on horizontal and vertical activity. The group treated with sodium nitrite significantly decreased the number of relative units compared to saline group on horizontal and vertical activity. The groups with sodium nitrite and Tacrine increased the number of relative units on horizontal and vertical activity compared to sodium nitrite group. The group with sodium nitrite and 30 mg/kg Metrifonate increased the number of relative units on horizontal activity only. The rats with sodium nitrite and 50 mg/kg Metrifonate slithly increased horizontal and vertical activity compared to hypoxia group. The animals with sodium nitrite and 80 mg/kg Metrifonate significantly increased the number of relative units on horizontal and vertical activity. Our results allow us to conclude that sodium nitrite induced hypoxia impaired brain functions, horizontal and vertical locomotor activity in the animals. Tacrine and metrifonate can partly to antagonize inhibitory effects of sodium nitrite on exploratory activity in rats. The effect of Tacrine is better than Metrifonate on moving activity in rats with hypoxia.