WP01 - Behavioural analysis of animal models

The main behavioural tests are selected on the basis of their validation as adequate models of particular constructs, such as impulsivity, inhibition, attention, reinforcement sensitivity and novelty seeking of central importance to this proposal. Other important criteria include the translational applicability of the tests to humans and also mice for genetic studies. Many of the tests for rats have already been implemented and studied intensively, including extensive analysis of underlying neural and neurochemical mechanisms (e.g. 5 choice reaction time test). A major methodological deliverable would be a parallel behavioural testing battery for rats and mice, appropriate for comparison with human neuropsychological tests.

The objectives of WP1 are as follows:

• Using a selective breeding strategy in rats to increase the frequency of an impulsive trait and to investigate its possible genetic basis using molecular methodology.
• Characterising the phenotype more fully at the behavioural level in the rat, investigating its possible relationship to other hypothetical traits in the human WP, including sensitivity to reward, appetitive and aversive conditioning, novelty seeking, and other forms of impulsivity, including impairments in delayed gratification.
• Initiating a parallel strategy in mice using similar behavioural screens, and comparing inbred strains to identify candidate genes using available databases (e.g. WebQTL) and bioinformatics methodology.
• These two strategies will allow a powerful convergence for establishing genetic-trait correlations and eventually identifying candidate genes for a) comparative analysis with human data, and b) testing using targeted gene manipulation in mice and rats.

WP leader is Professor Dr. Dai Stephens, University of Sussex. Dai Stephens and his colleagues of the Cambridge laboratory (Robbins, Everitt, Dalley) are world leaders in the establishment of rat models of human neuropsychological tests, and have had considerable success in inventing rat analogues of standard human behavioural test batteries for the evaluation of reward- and punishment-related processes.