Neuronal adenosine A_2Areceptors signal ergogenic effects of caffeine

Abstract

Ergogenic aid is a substance or method used for enhancing exercise and sports performance. Caffeine is the most used ergogenic aid for athletes, but the mechanisms are still unknown. Forty-two adult female (19±0.6 g) and 40 male mice (24±0.4 g) from a global and forebrain A2AR knockout and colony (FMUC, University of Coimbra) underwent an open field and ergospirometry exercise test. Caffeine (15 mg/kg, i.p.) and SCH 58261 (1 mg/kg, i.p.) were administered 15 minutes before the animals ran to exhaustion. We also evaluate the estrous cycle and infrared temperature (rest and recovery). Caffeine was psychostimulant in wild type females and males, but we observed this expected effect of SCH-58261 only in males. Caffeine and SCH-58261 were also ergogenic for wild type animals, that is, they increased running power and maximal O2 consumption (O2max). The psychostimulant and ergogenic effects of caffeine and SCH-58261 disappeared in A2AR knockout females (global) and males (forebrain). The estrous cycle did not influence any evaluated parameters, as well as exercise-induced hyperthermia was similar between savages and knockouts. Our results suggest that the neuronal A2AR receptors signal the ergogenic effects of caffeine in female and male mice.

Deletion of CD73 increases exercise power in mice

“…In conclusion, we now show the critical participation of CD73 in developing fatigue by continuing exercise at maximum intensities. This fully mimics the impact of forebrain A 2A R in controlling fatigue [8], in line with the prominent contribution of central effects of adenosine to control fatigue [26–28].…”

“…Running power is the sum (Σ) of all stages of the exercise test, and critical power is the running power performed above . is the maximum capacity to capture (respiratory), transport (cardiovascular), and consume (muscles) oxygen [8]. The respiratory exchange ratio (RER) is the rato between the amount of carbon dioxide producton and the consumed oxygen [8].…”

“…Adenosine is also a neuromodulator in brain circuits [5] that causes drowsiness and tiredness at rest [5,6] and is a candidate molecule to signal central exercise fatigue [7–9]. The observations that the ergogenic effects of caffeine in rodents are mimicked by selective antagonists of adenosine A 2A receptors (A 2A R) and abrogated in forebrain A 2A R knockout mice [8] and eliminated upon intracerebroventricular administration of the A 2 R agonist, NECA [9], strongly implies central A 2A R as critical regulators of the impact of adenosine on exercise performance.…”

Neuronal adenosine A2A receptors signal ergogenic effects of caffeine

“…Caffeine increases endurance 1 , 8 – 12 , intermittent 7 , 13 , 14 and resistance 4 , 15 exercise in humans. In rodents, its ergogenic effects are conserved because caffeine increases running time on the treadmill at constant 16 , 17 and accelerated speeds 18 , 19 . Sports sciences promote nonselective phosphodiesterase (PDE) inhibition 7 , 8 and increased calcium mobilization 2 , 7 , 8 as mechanisms for these ergogenic effects.…”

Caffeine decreases neuromuscular fatigue in the lumbar muscles – a randomized blind study

“…Caffeine also improves exercise performance expectations [26], cognitive and executive functions [19,29–31], and vigor [32] in exercising subjects. In animal studies, caffeine fails to be ergogenic in a mouse lacking neuronal A 2A R [33] and rats treated with 5’-N-ethylcarboxamidoadenosine (NECA), an adenosine analog [34,35].…”