Assessing cumulative severity in macaques used in neuroscience research

It is assumed that there are cumulative effects of repeated invasive procedures and contingent stressors on the welfare of non-human primates used in neuroscience research. The new EU Directive (2010/63/EU) on the use of animals in research emphasises the "lifetime experience" of animals and requires assessment of the "cumulative severity" of experiments. However, there are currently few data on the long-term impacts of repeated procedures to inform severity banding.

We aim to develop novel psychobiomarkers of cumulative stress based on our knowledge of major depressive disorder in humans and apply these measures to macaques involved in neuroscience research. We will take two main approaches: (1) measurement via qPCR of changes in leukocyte telomere length, and (2) measurement via MRI of structural and functional changes in the brain. These dependent variables will be taken at 6-monthly intervals from a group of 40+ animals involved in various types of neuroscience research; telomere measurements will also be made in 30+ control animals not subject to invasive procedures. Information on sources of possible stress (our independent variables, e.g. number and type of procedures, days on antibiotics or fluid control) will be collated for all animals in the study. Statistical modelling will be used to explore the relationships between potential stressors and our candidate psychobiomarkers.

These analyses will allow us to answer the question of whether the number and/or type of stressors a monkey has experienced predict changes in psychobiomarkers of cumulative stress. If cumulative effects of stressors are found, we will attempt to identify the shape of the relationship between stressors and our psychobiomarkers. Our results will: (1) provide a scientific basis for determining the cumulative severity rating of procedures, (2) reveal procedures that are most in need of refinement, and (3) permit adjudication on the relative costs of continued use of animals.

Bateson M (2015). Cumulative stress in research animals: Telomere attrition as a biomarker in a welfare context? BioEssays 38(2): 201-12 doi: 10.1002/bies.201500127

Bateson M, Nettle D (2015). Development of a cognitive bias methodology for measuring low mood in chimpanzees. PeerJ 3: e998 doi: 10.7717/peerj.998

Milham et al. (in press). An open resource for non-human primate imaging. Neuron.

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