Zebrafish: an animal model to study nicotinic drugs on spatial memory and visual attention

Neuronal nicotinic acetylcholine receptors (nAChRs) are involved in learning and memory in both humans and animals. For their physical characteristics, including small size, easiness to grow, and robustness of the species, zebrafish (Danio rerio) is rapidly becoming a popular model in bio-behavioral studies. Zebrafish are also easy to manipulate for researchers who are not practical users of traditional animal models. Here we describe two cognitive tasks which are sensitive to nicotinic drugs in a similar manner as rodents. Spatial memory is studied using a T-maze apparatus, where animals choose between two arms one of which contains a reservoir that offers a favorable habitat. Each fish receives two training trials at an interval of 24 h. The difference between the running time taken to reach the reservoir (and stay for at least 20 s) obtained during the first and the second trial is a measure of memory of the spatial location of reward. Visual attention is studied using a virtual object recognition test (VORT) where two geometrical 2D virtual shapes are presented stationary on two iPod screens. Shape recognition is scored in terms of exploration time whenever the zebrafish approach to the iPod area and direct their heads towards the shapes. To elucidate the involvement of nicotinic subtype receptors on memory, different selective nAChRs compounds (agonists and antagonists) are given through intraperitoneal (i.p.) route. All the compounds are tested also on swimming behavior to ascertain their possible interference with motor function. Here, we propose zebrafish as a useful tool to rapidly screen new nicotinic compounds active on cognitive disorders.