Scopolamine-induced learning impairment reversed by physostigmine in zebrafish

In this study, the effects of scopolamine, an acetylcholine muscarinic receptor antagonist, and physostigmine, an acetylcholinesterase inhibitor, on the learning ability and memory of zebrafish were evaluated using a passive avoidance response test. The zebrafish were trained to stay in a dark compartment to avoid a weight dropping into an acryl shuttle chamber with a central sliding door. The crossing time was increased significantly, from 30.7+/-40.8s to 179.3+/-27.3s in the training session and 179.9+/-28.0s in the test session carried out 2h later in the controls. When treatment with 200 microM scopolamine was administered for 1h prior to the training session, the crossing time did not increase. The scopolamine-induced learning deficit was ameliorated by pretreatment with 20 microM physostigmine for 1h prior to scopolamine treatment; the crossing time was similarly increased, as shown with the controls (60.9+/-11.5s, 130.9+/-27.5s, and 183.4+/-26.6s in the training session and 108.1+/-23.9s in the test session). When scopolamine treatment was administered after the training session, the crossing time in the test session was reduced significantly as compared to that noted in the third trial of the training session, which was also ameliorated by physostigmine pretreatment. These results show that scopolamine impairs both the acquisition of passive avoidance response and retention of the learned response, and that physostigmine rescues the amnesic effects of scopolamine in zebrafish.