Rodent models in psychiatry: severity assessment and potential measures for refinement and reduction

• Applicants: Professor Dr. Peter Gass; Dr. Anne Stephanie Mallien
• Subject Area: Biological Psychiatry ; Sensory and Behavioural Biology
• Term: since 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 321137804

This project aims to integrate all the results obtained on severity assessments into different data-scientific analyses from all project groups, in order to determine the most robust parameters and the direct comparability of all models from the FOR 2951 consortium, and to search for refinement strategies as well. We contribute the part on severity assessment of mice and rats in psychiatric research. Our measurements include the common parameters used to determine stress, such as behavioural abnormalities and physiological effects like stress hormone release, body weight and heart rates. Using a newly developed data science approach, we aim to target the parameters that most robustly and meaningfully represent stress in animals. This investigation takes place within the psychiatric models, but also in an overall comparison with the rest of the research group. In this way, it can be clarified, for example, which measurement variables are particularly suitable and whether other parameters may be relevant for psychiatric animal research than for other models. In addition, we are planning several meta-analyses on the particularly promising measurement parameters, such as body weight, burrowing or nest-building behaviour, in order to specifically check their robustness and ultimately also their generalisability. We will facilitate the comparison of previous results within the framework of FOR 2591 and will be able to directly compare the results using new statistical methods, for example the Relative Severity Assessment Score. This will allow us to compare methods from psychiatric research with those from other neuroscientific research and, moreover, on the basis of animal-specific parameters. This is done both for whole models, but also at the individual animal level. In a multi-laboratory approach, we have, on the one hand, carried out implantation stress for telemetry in the new FOR 2591 homecage system, and on the other hand, in parallel to the other parts of the project, investigated classical methods in psychiatric research, such as the forced swim test and fear conditioning. We expect a very high comparability between the models due to the almost identical measurement in the pending analyses. In addition, we are investigating the possibility of using the homecage system to avoid invasive implantation in the future and to use automated analyses of behaviour over long periods of time. As part of the implantation project, we are also contributing to studies on the refinement of analgesics. In addition, we participate in systematic and scoping literature reviews. We will use our database on the Forced Swim Test to make statements about the use of the test itself, the protocols and possible approaches to refinement of the test. We will also participate in the analysis of literature on water and food restriction.

• DFG Programme: Research Units
• Subproject of: FOR 2591: Severity assessment in animal-based research