Caffeine stimulates locomotor activity in the mammalian spinal cord via adenosine A1 receptor-dopamine D1 receptor interaction and PKA-dependent mechanisms

Abstract

Caffeine is a potent psychostimulant that can have significant and widely variable effects on the activity of multiple neuronal pathways. The most pronounced caffeine-induced behavioral effect seen in rodents is to increase locomotor activity which has been linked to a dose-dependent inhibition of A1 and A2A receptors. The effects of caffeine at the level of the lumbar spinal central pattern generator (CPG) network for hindlimb locomotion are lacking. We assessed the effects of caffeine to the locomotor function of the spinal CPG network via extracellular ventral root recordings using the isolated neonatal mouse spinal cord preparation. Addition of caffeine and of an A1 receptor antagonist significantly decreased the cycle period accelerating the ongoing locomotor rhythm, while decreasing burst duration reversibly in most preparations suggesting the role of A1 receptors as the primary target of caffeine. Caffeine and an A1 receptor antagonist failed to stimulate ongoing locomotor activity in the absence of dopamine or in the presence of a D1 receptor antagonist supporting A1/D1 receptor-dependent mechanism of action. The use of caffeine or an A1 receptor blocker failed to stimulate an ongoing locomotor rhythm in the presence of a blocker of the cAMP-dependent protein kinase (PKA) supporting the need of this intracellular pathway for the modulatory effects of caffeine to occur. These results support a stimulant effect of caffeine on the lumbar spinal network controlling hindlimb locomotion through the inhibition of A1 receptors and subsequent activation of D1 receptors via a PKA-dependent intracellular mechanism.

Energy drink - the prevalence of consumption and awareness regarding its associated potential health problems among commercial bus drivers in Ho, Ghana

“…This is in line with findings by Acevedo and colleagues [38], in which the majority (61%) of the study participants took energy drinks for enhanced performance. This suggests that most drivers overwork and need to be educated to take rests to reduce fatigue-related accidents on the roads.…”

Energy drink: the consumption prevalence, and awareness of its potential health implications among commercial drivers in the Ho Municipality of Ghana

“…The most predominant reason given by almost 8 out of 10 drivers (78.8%) was to enhance driving performance. This is in line with ndings by Acevedo and colleagues [38], in which the majority (61%) of the study participants took energy drinks for enhanced performance. This suggests that most drivers overwork and need to be educated to take rests to reduce fatigue-related accidents on the roads.…”

Bi-Directional Communication Between Neurons and Astrocytes Modulates Spinal Motor Circuits

“…Adenosine acts at A1 receptors to inhibit interneurons within the CPG, which in turn affects the frequency of motor output. Previous research has focussed on the astrocyte-to-neuron communication mechanisms that may impact motor circuits (Witts et al, 2012(Witts et al, , 2015Miles, 2015, 2017;Acevedo et al, 2016;Acton et al, 2018;Rivera-Oliver et al, 2018). In this study, we have identified previously unexplored neuron-to-astrocyte signaling mechanisms which may drive astrocyte-dependent modulation of the spinal cord locomotor CPG.…”

“…There is converging evidence that stimulating astrocytes pharmacologically, or ablating astrocytes with gliotoxins, reveals purinergic-dependent, glial-derived modulation of the spinal cord locomotor CPG (Dale and Gilday, 1996;Dale, 1998;Brown and Dale, 2000;Witts et al, 2012Witts et al, , 2015Acton and Miles, 2015;Acevedo et al, 2016;Acton and Miles, 2017;Acton et al, 2018;Rivera-Oliver et al, 2018). Although astrocytes in other CNS regions demonstrate the ability to utilize other transmitters, such as glutamate or GABA (Malarkey and Parpura, 2008;Christensen et al, 2018); there is a paucity of evidence to suggest that other gliotransmitters are involved in the astrocytic control of the locomotor CPG.…”