Effects of MK-801 and nicotine combinations on memory consolidation in CD1mice

Rationale: Recent experiments have shown that pre-trial administrations of nicotine to rats tested in a 16-arm radial maze attenuated the MK-801-induc ed deficit in both working and reference memory performance. Memory consoli dation can be influenced in laboratory animals, by post-training administra tion of drugs. Objective: In the present study we have investigated the eff ects on memory consolidation of CD1 mice exerted by: a) the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 [(+)-5-methyl-10,11 -dihydro-5H-dibenzo-[a,d]cyclo-hepten-5,10-iminemaleate] b) nicotine, and c ) combinations of MK-801 and nicotine. Methods: Different groups of mice we re injected intraperitoneally (IP) with the single drugs and with their com binations, immediately after training in a passive avoidance task. Addition al groups of animals were also injected 2 h post-training with the highest effective dose of MK-801 (0.3 mg/kg), with the highest effective dose of ni cotine (0.5 mg/kg) or with the combination of an otherwise ineffective dose of MK-801 (0.1 mg/kg) with the highest effective dose of nicotine, respect ively. Their performances were compared with those of mice injected with sa line, with the vehicle of nicotine and with the other treatment combination s, respectively Results: The results showed that MK-801 exerted deleterious effects, while nicotine exerted facilitatory effects on mice performances. Further, an otherwise ineffective dose of MK-801 (0.1 mg/kg) antagonized t he facilitatory effects of nicotine (0.25 and 0.5 mg/kg). In the 2 h post-t raining injected groups the treatments were ineffective, showing that the i mmediate post-training drug administrations affected memory consolidation p rocesses. Conclusions: In conclusion, from the present research, it is evid ent that NMDA glutamate and nicotinic acetylcholine receptor systems intera ct in modulating memory consolidation in CD1 mice.