Table 3.

Characteristics and the main results of studies analysing the effect of dopamine on physical activity and exercise.

Source	Study Design, Sample Characteristics (n, Sex, Age in Years), Country	Outcome Measures (PA)	Dopamine-Related Exposure	Main Findings
Maskin et al. [51]	Experimental study, 13 patients (9 men, 4 women) with severe chronic congestive heart failure, mean age 59 (range 48–72), USA.	Bicycle ergometer. The initial workload was 25 W for 3 min, and this load was increased every 3 min by 12.5 W until exhaustion.	Drug exposure: Dopamine was infused at an initial rate of 2 µg/kg/min for 15 min	DA exerted a slight chronotropic effect but did not improve ventricular performance during maximal exercise.
Boetger & Ward [52]	Controlled trial, 5 healthy males, USA.	A series of square-wave sub-anaerobic work-rate step tests on a bicycle ergometer was administered to each participant on 2 days.	Drug exposure: 3 µg/kg/min of dopamine at least 10 min before the dopamine test to ensure equilibration	Steady-state VE, VCO2. And VO2 were unchanged by dopamine infusion, both during unloaded pedalling and at the heavier workload.
Lundby et al. [53]	RCT, 12 sea-level natives (5 women, 7 men), aged 26 ± 1.4, Denmark, Switzerland, and Italy.	Two consecutive maximal exercise bouts, separated by an interval of 1 h, were performed on 4 separate occasions: at sea level and on day 1 (HA1, 24 h after arrival), day 3 (HA3), and day 5 (HA5) at high altitude. Five-minute warm-up at 120 W on a Monark 848 cycle ergometer and maximal exercise test. The protocol was designed to exhaust the participants within 3–5 min.	Drug exposure: 30 mg of domperidone (orally)	Hypoxic exercise in humans activated D2-receptors, resulting in a decrease in circulating levels of noradrenaline. However, dopamine D2-receptors were not involved in the hypoxia-induced decrease at the maximal heart rate.
Watson et al. [54]	Experimental randomized double-blind study, 9 healthy males, cyclists or triathletes, aged 22.7 ± 4.3, Belgium.	Constant cycle exercise for 60 min at a workload corresponding to 55% Wmax, followed by a TT to measure performance. The TT required the participants to complete a predetermined amount of work equal to 30 min at 75% Wmax as quickly as possible.	Drug exposure: Placebo or 2 × 300 mg bupropion	Performance in warm conditions is enhanced by acute administration of a dual dopamine/noradrenaline reuptake inhibitor.
Janssen et al. [43]	Prospective placebo-controlled randomized study, 13 healthy males, aged 23 ± 3, Belgium.	Each participant underwent a physician-supervised standard incremental CPET until the symptom-limited maximum. The work rate was increased by 30 W per minute after 1 min pedalling at 0 W.	Drug exposure: Dopamine (3 µg/min/kg) or placebo infusion (0.9% NaCl)	Inhibition of peripheral chemoreflex function with dopamine decreased the VE/VCO2 slope during dynamic exercise, with no change in aerobic exercise capacity.
Tedjasaputra et al. [55]	Experimental study with placebo control, 12 healthy males, aged 25 ± 6, Canada.	Two incremental staged cycling exercise sessions. The initial power output was set to 50 W, and the power output was increased by 25 W every 2 min until the ventilatory threshold was reached.	Drug exposure: Placebo or a DA receptor blocker (metoclopramide 20 mg)	DA blockade did not change O2 consumption, CO2 production, or respiratory exchange ratio at different exercise intensities. DA blockade decreased maximal cardiac output, VO2max, and TTE. Blocking DA receptors appeared to be detrimental to exercise performance.
Connell et al. [56]	Double-blind, placebo-controlled, repeated-measures randomized crossover study, 12 trained cyclists (7 women, 5 men), mean age 25 (19–45), New Zealand.	Three experimental trials involving 180 min of continuous cycling at a work rate equivalent to 60% of maximal aerobic capacity. A minimum of 5 d between crossover phases was enforced.	Drug exposure: DRI (40 mg methylphenidate), NRI (8 mg reboxetine), and placebo	DA reuptake inhibition and norepinephrine reuptake inhibition prevented fatigue-related decrements in the peak velocity of prosaccades.
Rosso et al. [44]	Cohort, 1635 sedentary adults at risk for disability, 65.9% women, aged 78 ± 5.2, USA.	PA was calculated from accelerometry (min/d) at baseline, 6, 12, and 24 months. PA versus health education for an average of 2.6 years. PA intervention consisted of walking (goal of 150 min/week), strength, flexibility, and balance training.	No drug exposure: Single nucleotide polymorphisms of dopamine-related genes (dopamine receptor (DR) D1, DRD2, DRD3, and catechol-O-methyltransferase)	Higher dopamine signalling may support changes in PA during an intervention.

Abbreviations: DA, dopamine; VE, breath-by-breath ventilation; VCO₂, CO₂ production; VO₂, O₂ consumption; HA1, HA3, and HA5, days 1, 3 and 5 respectively at high altitude; ACTH, adrenocorticotropic hormone; CPET, cardiopulmonary exercise testing; DR, dopamine receptor; PA, physical activity; SNPs, single nucleotide polymorphisms; TT, trial time; TTE, time to exhaustion; MVPA, minutes of moderate-to-vigorous physical activity.