MK-801-induced learning impairments reversed by physostigmine and nicotine in zebrafish

Previous studies have demonstrated that N-methyl-D-aspartate (NMDA) receptors and acetylcholine receptors are related to learning and memory in rat and mice. In this study, we examined the effects of MK-801, a non-competitive NMDA receptor antagonist, on learning and memory in zebrafish using a passive avoidance test. We further tested whether or not nicotine, a nicotinic acetylcholine receptor agonist, and physostigmine, an acetylcholinesterase inhibitor, reverse the effects of MK-801. Crossing time was increased significantly in the training and test sessions for the controls. When 20 mM MK-801 was administered prior to the training session, the crossing time did not increase in either session. The MK-801-induced learning deficit was rescued by pretreatment with 20 mM physostigmine, and crossing time was increased in the training and test sessions compared to the MK-801-treated zebrafish. Further, the MK-801-induced learning deficit was prevented by pretreatment with 20 mM nicotine, and crossing time was increased in the training session but not in the test session. These results show that MK-801 induced a learning deficit in zebrafish that was prevented by pretreatment with nicotine and physostigmine.