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P1‐019: Effects of tacrine and dimebon on scopolamine‐ and dizocilpine‐induced memory impairment in mice
Author(s) -
Salimov Ramiz,
Kachenko Sergey T.
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.604
Subject(s) - tacrine , ampa receptor , acetylcholinesterase inhibitor , acetylcholinesterase , donepezil , dizocilpine , pharmacology , neuroscience , psychology , neurotransmission , nmda receptor , anesthesia , medicine , chemistry , receptor , dementia , disease , biochemistry , enzyme
Background: Interaction between glutamate and acetylcholine brain systems is considered to be implicated in the development of Alzheimer disease. A decrease in the glutamate AMPA receptor-mediated neurotransmission was found in mice carrying human mutations in genes for amyloid precursor protein and presenilin-1suggesting contribution of AMPA receptors into pathogenesis of Alzheimer disease. In the present study we compared effects of acetylcholinesterase inhibitor tacrine with those of both acetylcholinesterase inhibitor and AMPA-receptor agonist dimebon on scopolamineand dizocilpine-induced memory impairment in one-trial passive avoidance and novel object recognition tests. Methods: Male BALB/c mice were used in the step-through passive avoidance test. The apparatus consisted of light and dark compartments connected via guillotine door. During a training trial, animals received punishment (0.6 mA, 3 c) after entry into the dark compartment. A retention trial was performed 24 h later with no punishment and cut-off time of 5 min. The novel object recognition test was done in 4-arm closed maze with male SHK mice. During the training trial, a plastic cup was placed into each arm and a mouse was given 13 attempts to visit the arms. Before a similar retention trial performed 1h later, two cups in opposite arms were replaced with two identical glass flacks. Animal behavior was monitored by computer videosystem and analyzed by Any-maze software. Recognition index was calculated as time spent in arms with novel objects divided by time spent in all arms. All drugs were administered i.p. 30 minutes before training trial, except for dimebon, which was injected 5 min before the test. We used the minimal pro-amnesic doses of scopolamine and dizocilpine, which were 0.3 and 0.1 mg/kg in the passive avoidance test and 1 and 0.2 mg/kg in the novel object recognition test. Results: Tacrine (10 mg/kg) significantly attenuated scopolamine-induced amnesia and did not alter dizocilpineinduced amnesia in both tests. Dimebon (0.1 mg/kg) markedly reduced scopolamine-induced amnesia and produced a slight but statistically significant recovery from dizocilpine-induced amnesia in both tests. Conclusions: The results show that a novel anti-Alzheimer drug should act on several neurotransmitter systems in the brain, particularly on acetylcholine and AMPA-receptor systems.