Development and validation of a rodent touchscreen battery for assessing motivation and affective state

Lead Research Organisation: University of Cambridge
Department Name: Psychology

Abstract

Mental illness currently contributes the highest global economic burden of all chronic diseases. Neurological disorders such as stroke and dementia also reflect a huge burden to society that is expected to increase as the population ages. Impaired motivation and emotional reactivity are core symptoms of these disorders, typically occurring early in the disease course and persisting or worsening as the illness progresses. These symptoms are particularly debilitating for both patients and their caregivers; for example, those caring for an Alzheimer's patient reported that these symptoms are more distressing than the memory loss primarily associated with the disease. However, at present, no targeted pharmacotherapies exist for these symptoms, suggesting that there is a great need for further research in this area.

Animal models are essential in the search for knowledge about, and in the development of new treatments for, these conditions. However, the way in which symptoms involving emotion and motivation are assessed in animals is often overly simplistic and differs greatly from how these symptoms are assessed in humans. For example, most current studies in this area investigate these aspects of behaviour using techniques that generate negative emotions in the animals (e.g., fear and anxiety) via inescapable electrical shock, restraint or immersion in water. This makes comparison to humans, and therefore the development of effective treatments, very difficult.

We have developed a touchscreen-based system that is now well-established for assessing learning, memory and attention in mice and rats. The tests simply require animals to nosepoke images on the screen with correct responses rewarded with a drop of milkshake. In this project we propose to develop an analogous touchscreen-based system for the assessment of emotion and motivation in rodents.

The development of a touchscreen-based system for the assessment of emotion and motivation will allow for the neurobiological investigation of these critical aspects of behaviour in a non-stressful fashion. The new methods will also allow us to measure the effectiveness of new drugs designed to alleviate the symptoms of negative emotion and lack of motivation seen in many human neuropsychiatric and neurodegenerative diseases without causing any distress to the animals involved. The touchscreen assessments are also designed to be very similar to those used in human clinical trials, which will increase the probability that a positive effect seen in the animals will translate to a positive effect in humans. Furthermore, this assessment system will be very useful for routine evaluation of animal welfare and also in determining if changes in husbandry techniques and housing environment lead to reduced stress, thereby allowing us to objectively improve the quality of life for animals in the laboratory more generally. Widespread adoption of touchscreen-based assays to assess emotion and motivation could substantially decrease the severity of testing for at least 30,000 rodents annually.

Technical Summary

Motivation and emotional processing are compromised in numerous disorders (e.g., Alzheimer's disease, schizophrenia and depression) and thus are frequently assessed in rodent disease models. However, most current tests fall into the moderate severity band as they are highly aversive and involve restraint, inescapable electric shock or forced swimming.

The rodent touchscreen testing system is well-established as a versatile cognitive assessment tool that avoids aversive conditions, instead using rewards such as milkshake. We propose to develop a suite of rodent touchscreen-based assays for motivation and emotion and show that they can replace higher-severity assays (refinement) by validating their efficacy with a series of experiments focused on three manipulations known to affect different aspects of these constructs: (1) a standardised panel of drugs; (2) chronic exposure to the stress hormone corticosterone; and (3) ethologically-valid environmental manipulations. This will also demonstrate the utility of these tasks for assessing new drugs for benefits on emotional state, for measuring rodent stress and monitoring welfare, and for standardised assessment of new welfare manipulations such as environmental enrichment or changes in husbandry practises.

Aversive tasks to measure emotion and motivation are used extensively. Widespread adoption of touchscreen-based assays to assess emotion and motivation could decrease the severity of testing for at least 30,000 rodents annually. Touchscreen-based rodent tests are very similar to those used in humans, which greatly increases the probability of successful translation of treatments from the lab to the clinic, potentially reducing the number of animal experiments required. Additional advantages are increased precision of data through automation and computerisation and the possibility of conducting multiple tests in the same apparatus, both of which contribute to reduction.

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