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Rodent touchscreens and the quest for better models for depression

Emma Robinson

Professor Emma Robinson

6 March 2019

Depression is a mood disorder which, according to the American Psychiatric Association, will affect 1 in every 6 people during the course of their lives. Antidepressant drugs are a common medical treatment, but since their accidental discovery over 50 years ago, few significant advances have been made - not least because of the lack of effective animal models.

Professor Emma Robinson’s group in the School of Physiology, Pharmacolog and Neuroscience at the University of Bristol used a TRACK (Translational Acceleration and Knowledge Transfer) Award from the Elizabeth Blackwell Institute to help develop a rodent version of a test to study how people process emotional information. The TRACK Award supports health related projects with translational or commercial potential which need a specific piece of work to secure further funding.

Prof. Robinson explained: “In a clinical context, depression is defined by how the patient feels, and their own experience of the disease, which is unsurprising tricky to replicate in animal models. So, translating findings from basic research to a clinical setting can be hard”.

Prof. Robinson’s group aimed to overcome these issues by modifying a test they’d already developed to make it faster, and more useful to industry. The test looks at how much value an animal attributes to a specific reward-linked experience, and the effects of different emotions on learning and memory. This non-clinical method of assessing the safety of novel compounds could be modified and automated to increase its usefulness to pharmaceutical companies. If this non-clinical method for assessing antidepressant efficacy, and the safety of novel compounds could be modified and automated, it would increase its usefulness to pharmaceutical companies.

Firstly, the equipment the group used to modify rat behaviour using rewards was upgraded to provide stimuli on touchscreens that the rats can use. The rats were trained successfully to respond to specific images on the touch screen. However, training the rats to the touchscreen took much longer than was anticipated.

Despite this, initial testing of the touchscreen experiments provided proof of concept data; the rats using the touchscreen equipment generated results consistent with their previous findings. But the time required to train the animals, and the subsequent extension of the experimental timescales possibly outweighed any benefits from automation. So, the team then designed and tested a version using flavoured sugar solutions. Work is ongoing to refine these methods to further improve their format and to deliver more reliable results.

Professor Robinson is very optimistic for the future, however: “Although the current state of the project is ongoing rather than completed, we have been able to move forward and competed some very valuable pilot data. As we now also have two major grants funded, the work will progress over the next few years.

“The support from Elizabeth Blackwell Institute was very helpful in enabling us to purchase the equipment needed to undertake this work and we would not have been able to get this type of funding from any other source.”

The project has also had other benefits, with the establishment of a number of fruitful collaborations. Prof. Robinson has also established new collaborations associated with this project.

“A project specific collaboration has been established with Dominic Dwyer in Cardiff looking at the automation of the ABT and an alternative method which utilises his expertise in flavour preference studies in rodents. We have also developed a more indirect collaboration with Jon Brooks who is based in CRIC which links to the touchscreen technology purchased through this TRACK award. We are currently working on a pilot project to develop and test a novel, translational task for attention studies which should be of commercial interest in the future.”

 

Further information

A translational rodent assay of affective biases in depression and antidepressant therapy.

Distinct Neuropsychological Mechanisms May Explain Delayed- Versus Rapid-Onset Antidepressant Efficacy.

Further validation of the affective bias test for predicting antidepressant and pro-depressant risk: effects of pharmacological and social manipulations in male and female rats.

Using the affective bias test to predict drug-induced negative affect: implications for drug safety.

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