ABSTRACT
Introduction: Caffeine and the selective A2A receptor antagonist SCH58261 both have ergogenic properties, effectively reducing fatigue and enhancing exercise capacity. This study investigates in male Swiss mice the interaction between adenosine A2A receptors and dopamine D2 receptors controlling central fatigue, with a focus on the striatum where these receptors are most abundant. Methods: We employed DPCPX and SCH58261 to antagonize A1 and A2A receptors, caffeine as a non-competitive antagonist for both receptors, and haloperidol as a D2 receptor antagonist; all compounds were tested upon systemic application and caffeine and SCH58261 were also directly applied in the striatum. Behavioral assessments using the open field, grip strength, and treadmill tests allowed estimating the effect of treatments on fatigue. Results and discussion: The results suggested a complex interplay between the dopamine and adenosine systems. While systemic DPCPX had little effect on motor performance or fatigue, the application of either caffeine or SCH58261 was ergogenic, and these effects were attenuated by haloperidol. The intra-striatal administration of caffeine or SCH58261 was also ergogenic, but these effects were unaffected by haloperidol. These findings confirm a role of striatal A2A receptors in the control of central fatigue but suggest that the D2 receptor-mediated control of the ergogenic effects of caffeine and of A2A receptor antagonists might occur outside the striatum. This prompts the need of additional efforts to unveil the role of different brain regions in the control of fatigue.
ABSTRACT
Mental fatigue alters cognitive performance and autonomic regulation. The neurovisceral model proposes that forebrain structures associated to cognitive control abilities influences heart rate variability. Parasympathetic mediated heart rate variability indices reduction during mental fatigue experience is well-described in previous studies, but the contribution of heart-brain axis to cardiac autonomic adaptation remains unknown. This study investigates the association between root mean square of successive differences between RR intervals (rMSSD) and N2 event-related potential component during visual prolonged odd/ball task (â 60min.). The comparison between task blocks shows that rMSSD (p = 0.004) and N2 (p = 0.04) decreased with time on task. Pearson correlation shows that ΔrMSSD is associated with ΔN2 (p = 0.007). Our results support the neurovisceral integration model showing that cognitive control contributes to cardiac autonomic tone adaptation during mental fatigue experience.
