Pharmacological analyses of learning and memory in zebrafish (Danio rerio)

Abstract

Over the last decade, zebrafish (Danio rerio) have become valuable as a complementary model in behavioral pharmacology, opening a new avenue for understanding the relationships between drug action and behavior. This species offers a useful intermediate approach bridging the gap between in vitro studies and traditional mammalian models. Zebrafish offer great advantages of economy compared to their rodent counterparts, their complex brains and behavioral repertoire offer great translational potential relative to in vitro models. The development and validation of a variety of tests to measure behavior, including cognition, in zebrafish have set the stage for the use of this animal for behavioral pharmacology studies. This has led to research into the basic mechanisms of cognitive function as well as screening for potential cognition-improving drug therapies, among other lines of research. As with all models, zebrafish have limitations, which span pharmacokinetic challenges to difficulties quantifying behavior. The use, efficacy and limitations associated with a zebrafish model of cognitive function are discussed in this review, within the context of behavioral pharmacology.

Keywords: Learning; Memory; Pharmacology; Zebrafish.

Figure 1

Diagram of apparatus used to measure startle response. Fish were tested in 8 cylindrical chambers separated by opaque dividers. A pushsolenoid delivered a tap as a startle stimulus at 1 min intervals (10 total trials). A camera mounted overhead acquired video, which was imported into EthoVision tracking software to measure swimming distance.

Figure 2. Diagram of the zebrafish 3-chamber task for assessing learning and memory. (Eddins et al., 2009)

Figure 3. Correlation of percent correct in the 3-chamber task with brain DOPAC concentration. (Eddins et al., 2009)

Figure 4. Nicotine effect improving A) spatial discrimination and B) spatial alternation in the 3-chamber task (mean±SEM). (Levin and Chen 2004, Levin et al., 2006)

Figure 4. Nicotine effect improving A) spatial discrimination and B) spatial alternation in the 3-chamber task (mean±SEM). (Levin and Chen 2004, Levin et al., 2006)