Measuring Behavior 2005: Berghmans et al.

Zebrafish: A novel source of behavioral paradigms to allow high throughput drug discovery

S. Berghmans, J. Salzmann, P. Goldsmith and A. Fleming

DanioLabs Ltd., Cambridge Research Park, Cambridge, UK

The zebrafish model system is amenable to high throughput screening because of numerous advantages, including the relative ease of maintaining large stocks of animals; its high fecundity, which provides the investigator with large numbers of animals to analyze; and the rapid embryonic development ex utero, which facilitates experimental manipulation and allows the direct observation of tissue formation and organogenesis in vivo. The organization of the human genome and the genetic pathways controlling signal transduction and development are highly conserved in zebrafish. These properties have established the zebrafish as an excellent model system that is relevant to studies of human diseases. Recently, zebrafish has become the focus of neurobehavioral studies because it displays learning, memory and behavior phenotypes that are quantifiable and relate to those seen in man. It is also known that the zebrafish brain structure and function are similar to other vertebrates, lending further support to its use as a useful model for evaluating vertebrate behavior.

Our company’s goals are to commercialize zebrafish models of human disease and to discover candidate therapeutic compounds with the assays we develop. We have focused on establishing assays addressing neurobehavioral paradigms and behavioral quantification methods with which one can detect drug induced alterations in brain function of the embryo or the adult fish. These models range from basic behavior such as startle response or locomotor activity to more complex ones such as drug addiction or sleep. We plan to establish a collection of scalable behavioral paradigms highly relevant to high throughput and automatable screens to be used for drug discovery, drug reprofiling and safety pharmacology. Our latest progress in neurobehavioral test designs and their utility in drug screening using the zebrafish will be further discussed.

Paper presented at Measuring Behavior 2005 , 5^th International Conference on Methods and Techniques in Behavioral Research, 30 August - 2 September 2005, Wageningen, The Netherlands.