Effects of MK-801 and nicotine combinations on memory consolidation in CD1 mice

Abstract.

Rationale: Recent experiments have shown that pre-trial administrations of nicotine to rats tested in a 16-arm radial maze attenuated the MK-801-induced deficit in both working and reference memory performance. Memory consolidation can be influenced in laboratory animals, by post-training administration of drugs. Objective: In the present study we have investigated the effects 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-imine-maleate] b) nicotine, and c) combinations of MK-801 and nicotine. Methods: Different groups of mice were injected intraperitoneally (IP) with the single drugs and with their combinations, immediately after training in a passive avoidance task. Additional 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 nicotine (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, respectively. Their performances were compared with those of mice injected with saline, with the vehicle of nicotine and with the other treatment combinations, 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 the facilitatory effects of nicotine (0.25 and 0.5 mg/kg). In the 2 h post-training injected groups the treatments were ineffective, showing that the immediate post-training drug administrations affected memory consolidation processes. Conclusions: In conclusion, from the present research, it is evident that NMDA glutamate and nicotinic acetylcholine receptor systems interact in modulating memory consolidation in CD1 mice.