Effects of dizocilpine (MK-801) on circling behavior, swimming activity, and place preference in zebrafish (Danio rerio)

Glutamate transmission plays an important role in many behavioral systems, including motor activity, learning, and memory. The noncompetitive NMDA receptor antagonist (+)MK-801 has been shown to increase motor activity and impair learning and memory in a variety of tasks in rats, mice, and other species. In an attempt to characterize the effects of MK-801 on motor activity and cognitive performance in an emerging neurobehavioral model, the zebrafish (Danio rerio), we examined the effects of MK-801 on circling behavior, swimming activity, and latency to enter, as well as preference for, an enriched chamber (EC). In Experiment 1, the effects of a 37-min acute exposure to (+)MK-801 (0, 2.0, and 20.0 microM) on circling behavior were measured in a round observation chamber. (+)MK-801 was observed to increase circling behavior in a dose-dependent manner. In the second experiment, fish were treated with 0, 2, 20, or 200 microM (+)MK-801 for 1 h, and swimming activity was measured in a rectangular observation chamber for 60 min following dosing. The lowest dose of (+)MK-801 decreased swimming activity. In the third experiment, fish were treated with either 0 or 20 microM (+)MK-801 for 1 h each day over four consecutive days. The fish were tested in a modified T-maze to assess both latency to enter, and preference for, an EC 24, 27, and 48 h after the last treatment. The results showed that untreated fish exhibited a preference for the EC at the 27- and 48-h trials, but (+)MK-801-treated fish did not exhibit a preference for the EC at any trial. No significant reduction in latency to enter the chamber was found for either treated or control fish. Together, the results of these experiments suggest that NMDA receptor antagonism (1) increases circling behavior, (2) alters swimming activity, and (3) impairs place preference. These findings lend further support for the usefulness of the zebrafish for assessing the acute and chronic exposure effects of water-soluble compounds on motor and cognitive functions.