Pharmacological facilitation of physical activity behaviour: an experimental medicine approach

Physical inactivity is a global health problem. Despite a good understanding of the benefits of completing regular exercise, adherence rates at a population level are extremely low. An experimental medicine approach to health behaviour change was recently proposed, which prioritises an understanding of how, not just whether interventions are effective. The present study serves as the first application of this model to develop a physical activity behaviour change intervention. This thesis is comprised of eight studies in 6 experimental chapters, which are presented in two parts.

Part I is focussed on understanding whether changes in perceptual responses to exercise, caused by caffeine, are sufficient to elicit a change in physical activity behaviour. Chapter 4 utilised a single-subject experimental design as a preliminary trial. We provided the first experimental evidence that pharmacological intervention can influence physical activity choice behaviour by manipulating feelings during and around exercise. In chapter 5, a group trial corroborated many of the psychological and perceptual effects of caffeine observed in chapter 4, whilst a qualitative exploratory analysis of the factors underlying exercise choice revealed that perception of effort was the primary determinant of exercise preference. chapter 6 investigated the metabolic effects of caffeine during high-intensity interval training (HIIT). Providing evidence to suggest that caffeine can elicit a dual function of increasing non-exercise thermogenic activity, as well as increasing metabolic activity during HIIT, without an increase in perceptions of effort and discomfort.

The aim of Part II was to develop a preclinical model to measure the effects of pharmacological interventions on physical activity behaviour. In chapter 10 we determined an appropriate running wheel access paradigm. In chapter 11 we proved for the first time that caffeine does not elicit a significant increase in voluntary wheel-running activity during the active phase in mice. Whilst chapter 12 validated a method of pharmacologically inducing human sedentary-like behaviours in mice, and demonstrated the ability to completely reverse wheel-running suppression with caffeine administration.

In sum, this thesis offers translational models, able to detect psychological and behavioural effects of pharmacological intervention, providing a platform from which to test the effects of alternative drugs, for trials at a pre-clinical and human level, on physical activity behaviour in the future.