Abstract. The cholinergic system undergoes changes with aging and in Alzheimer's disease. The effects of the anticholinesterase drugs galantamine and donepezil were studied in a model with sodium nitrite-induced hypoxia in rats. The animals were trained in the shuttle-box active avoidance test and in step-through and step-down passive avoidance tests. In the active avoidance test, hypoxic rats showed a decrease in the number of avoidances in the learning session and in retention. The hypoxic rats receiving galantamine showed an increase in the number of avoidances during the learning session. The groups in hypoxia treated with donepezil had an increased number of avoidances in the learning session. In memory retention tests, significant differences were not observed in the hypoxic animals treated with galantamine or donepezil. In the step-through passive avoidance test, rats treated with galantamine had no change in the latency of reactions during the learning session and memory retention tests. In the step-down passive avoidance test, the animals treated with galantamine had increase latency of reactions during the learning and short-or long-memory retention tests. The hypoxic rats receiving donepezil had increased latency of reactions in the step-down short memory retention test. Our results suggest that galantamine and donepezil improve cognitive functions in a model of hypoxia.
BackgroundCholinesterase inhibitors and glutamate blockers are commonly used for the treatment of cognitive impairment in Alzheimer’s disease. The aim was to evaluate the effects of rivastigmine and memantine alone or in combination in rats with scopolamine-impaired memory.Method5 groups of rats were used: control, scopolamine (model), model with rivastigmine, model with memantine, and model with both drugs. Active avoidance test was performed and the number of conditioned responses, unconditioned responses and intertrial crossing were recorded. Passive avoidance tests step-through with criteria latency of reaction 180 s in the light chamber and step-down with criteria latency of reaction 60 s on the platform were done.ResultsControl rats learned the task and kept it on memory tests. Scopolamine treated rats failed to perform it. The rivastigmine, memantine and its combination groups showed increased CRs during learning and memory retention tests. In both passive avoidance tests an increased latency of reaction was observed in the drug treated groups.ConclusionThe combination of both drugs rivastigmine and memantine is more effective than the use of the single drug in cognitive impaired rats. Cholinesterase inhibitors and NMDA blockers may be combined in the treatment of different kind of dementias.
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