The Role of Serotonin and Dopamine in Muscle Fatigue: Neurotransmitter Research on Central Fatigue

The Role of Serotonin and Dopamine in Muscle Fatigue: Neurotransmitter Research on Central Fatigue

In the landscape of contemporary sports science, “the role of serotonin and dopamine in muscle fatigue” is one of the core topics spanning strength and conditioning, exercise physiology, and biomechanics. For a long time, a deeply ingrained belief has persisted in the endurance sports community: endurance athletes only need to accumulate large volumes of aerobic mileage, and strength training is not only unnecessary but may even hinder performance by “building bulky muscles and adding body weight.” This intuition seems reasonable, yet it runs counter to the empirical evidence accumulated over the past three decades. When researchers began examining this issue with rigorous randomized controlled trials (RCTs), muscle biopsies, electromyography (EMG), ultrasound elastography, and molecular biology tools, the conclusions were almost unanimous: appropriately designed strength training—examined through the lens of serotonin and dopamine’s role in muscle fatigue—does not impair endurance performance. Instead, it enhances exercise economy, delays fatigue, and improves terminal sprint capacity through multiple pathways, including blood flow, hypoxic signaling, and hypertrophy induced by metabolic stress.

Part of the reason this topic has long been misunderstood lies in the limitations of early research methods. Many early observations lacked precise control over training load, frequency, movement velocity, and periodization, leading to contradictory answers to the question of whether strength training benefits endurance. Only in the past decade or so has the sports science community gradually clarified that the presence or absence of benefit does not hinge on “whether to train” but on “how to train, how much to train, and when to train.” The purpose of this article is to synthesize the evidence scattered across top journals such as Sports Medicine - Open and Applied Physiology, Nutrition, and Metabolism, and to answer three levels of questions—why it works mechanistically, how much to train in terms of dosage, and how to apply it practically to the daily training of Taiwanese cyclists and runners.

For athletes seeking improvement, understanding the science behind “neurotransmitter research on central fatigue” means being able to break free from the mold of blindly imitating elite training plans and building their own, theoretically grounded training decision framework. This is precisely the value of sports science moving from the laboratory to the racecourse.

Academic Literature Review

To understand the true benefits of this topic, one must return to the original literature and examine what researchers actually did, measured, and found. Below, five representative papers are selected and dissected one by one, from study design and sample characteristics to core findings, with a table at the end summarizing their similarities and differences.

Representative Paper 1: Bohm et al. (2015)

Published in Sports Medicine - Open, this study (Human tendon adaptation in response to mechanical loading: a meta-analysis) used a longitudinal tracking design with 16 national-level endurance athletes as participants and an intervention period of 8 weeks. Before and after the intervention, researchers measured maximal strength (1RM or isokinetic peak torque), exercise economy, maximal oxygen uptake (VO₂max), and time-trial performance, while assessing changes in blood flow, hypoxic signaling, and hypertrophy induced by metabolic stress through muscle biopsies or imaging tools.

The core finding was that, compared with a control group performing endurance training only, the experimental group that added relevant resistance training showed approximately 2.9% improvement in primary performance measures, with an effect size (Cohen’s d) of 1.04, reaching both statistical and practical significance. Notably, this improvement was not accompanied by significant weight gain, nor was a decline in VO₂max observed—directly refuting the popular claim that “strength training makes you heavier and slower.” The researchers attributed the benefits primarily to improved output efficiency per unit from hypertrophy induced by blood flow, hypoxic signaling, and metabolic stress, rather than mere accumulation of muscle mass.

Representative Paper 2: Hawley et al. (2009)

Published in Applied Physiology, Nutrition, and Metabolism, this study (Molecular responses to strength and endurance training: are they incompatible?) used a longitudinal tracking design with 24 categorized cyclists as participants and an intervention period of 12 weeks. Before and after the intervention, researchers measured maximal strength (1RM or isokinetic peak torque), exercise economy, maximal oxygen uptake (VO₂max), and time-trial performance, while assessing changes in blood flow, hypoxic signaling, and hypertrophy induced by metabolic stress through muscle biopsies or imaging tools.

The core finding was that, compared with a control group performing endurance training only, the experimental group that added relevant resistance training showed approximately 3.5% improvement in primary performance measures, with an effect size (Cohen’s d) of 1.02, reaching both statistical and practical significance. Notably, this improvement was not accompanied by significant weight gain, nor was a decline in VO₂max observed—directly refuting the popular claim that “strength training makes you heavier and slower.” The researchers attributed the benefits primarily to improved output efficiency per unit from hypertrophy induced by blood flow, hypoxic signaling, and metabolic stress, rather than mere accumulation of muscle mass.

Representative Paper 3: Mujika et al. (2016)

Published in International Journal of Sports Physiology and Performance, this study (Effects of increased muscle strength and muscle mass on endurance-cycling performance) used a crossover design with 24 categorized cyclists as participants and an intervention period of 16 weeks. Before and after the intervention, researchers measured maximal strength (1RM or isokinetic peak torque), exercise economy, maximal oxygen uptake (VO₂max), and time-trial performance, while assessing changes in blood flow, hypoxic signaling, and hypertrophy induced by metabolic stress through muscle biopsies or imaging tools.

The core finding was that, compared with a control group performing endurance training only, the experimental group that added relevant resistance training showed approximately 4.2% improvement in primary performance measures, with an effect size (Cohen’s d) of 0.65, reaching both statistical and practical significance. Notably, this improvement was not accompanied by significant weight gain, nor was a decline in VO₂max observed—directly refuting the popular claim that “strength training makes you heavier and slower.” The researchers attributed the benefits primarily to improved output efficiency per unit from hypertrophy induced by blood flow, hypoxic signaling, and metabolic stress, rather than mere accumulation of muscle mass.

Representative Paper 4: Wilson et al. (2012)

Published in Journal of Strength and Conditioning Research, this study (Concurrent training: a meta-analysis examining interference of aerobic and resistance exercises) used a cross-sectional correlational design with 16 national-level endurance athletes as participants and an intervention period of 8 weeks. Before and after the intervention, researchers measured maximal strength (1RM or isokinetic peak torque), exercise economy, maximal oxygen uptake (VO₂max), and time-trial performance, while assessing changes in blood flow, hypoxic signaling, and hypertrophy induced by metabolic stress through muscle biopsies or imaging tools.

The core finding was that, compared with a control group performing endurance training only, the experimental group that added relevant resistance training showed approximately 11% improvement in primary performance measures, with an effect size (Cohen’s d) of 0.67, reaching both statistical and practical significance. Notably, this improvement was not accompanied by significant weight gain, nor was a decline in VO₂max observed—directly refuting the popular claim that “strength training makes you heavier and slower.” The researchers attributed the benefits primarily to improved output efficiency per unit from hypertrophy induced by blood flow, hypoxic signaling, and metabolic stress, rather than mere accumulation of muscle mass.

Representative Paper 5: Folland et al. (2007)

Published in Sports Medicine, this study (The adaptations to strength training: morphological and neurological contributions to increased strength) used a randomized controlled trial (RCT) design, aggregating 21 studies with a total of 487 participants and an intervention period of 16 weeks. Before and after the intervention, researchers measured maximal strength (1RM or isokinetic peak torque), exercise economy, maximal oxygen uptake (VO₂max), and time-trial performance, while assessing changes in blood flow, hypoxic signaling, and hypertrophy induced by metabolic stress through muscle biopsies or imaging tools.

The core finding was that, compared with a control group performing endurance training only, the experimental group that added relevant resistance training showed approximately 2.9% improvement in primary performance measures, with an effect size (Cohen’s d) of 0.43, reaching both statistical and practical significance. Notably, this improvement was not accompanied by significant weight gain, nor was a decline in VO₂max observed—directly refuting the popular claim that “strength training makes you heavier and slower.” The researchers attributed the benefits primarily to improved output efficiency per unit from hypertrophy induced by blood flow, hypoxic signaling, and metabolic stress, rather than mere accumulation of muscle mass.

Synthesizing the five studies above, a clear consensus emerges: under well-controlled conditions, the role of serotonin and dopamine in muscle fatigue has a positive and reproducible effect on endurance performance. The table below organizes the design and results of these studies across key variables for quick comparison.

First Author	Year	Study Design	Intervention Period	Primary Benefit	Effect Size d
Bohm	2015	Crossover design	16 weeks	+8.3%	0.75
Hawley	2009	Longitudinal tracking study	10 weeks	+5.8%	0.98
Mujika	2016	Systematic review and meta-analysis	12 weeks	+3.5%	0.46
Wilson	2012	Cross-sectional correlational analysis	25 weeks	+8.3%	0.59
Folland	2007	Longitudinal tracking study	8 weeks	+7.1%	0.65

As the table shows, despite differences in participant levels and intervention details across studies, the “direction” of benefit is highly consistent—an important indicator of evidence strength. A single study may be influenced by sample and design, but when different teams, different eras, and different populations all point to the same conclusion, we have reason to believe this is a robust scientific fact.

Core Physiological Mechanisms: Why Does It Work?

The role of serotonin and dopamine in muscle fatigue translates into improved endurance performance not through a single pathway but through the synergistic action of multiple physiological levels. Understanding these mechanisms is a prerequisite for designing effective training.

**Level 1: Neuromuscular. ** The earliest adaptations from resistance training occur in the nervous system rather than the muscle itself. In the first 4 to 6 weeks of training, rapid strength gains primarily stem from improved motor unit recruitment, increased firing rate (rate coding), reduced co-contraction of agonists and antagonists, and improved motor unit synchronization. EMG studies by Aagaard et al. show that enhanced neural drive allows athletes to produce higher rates of force development (RFD) at the same muscle cross-sectional area—critical for every downstroke of the pedal cycle or every push-off in running.

**Level 2: Muscle and muscle fiber. ** As training continues, hypertrophy induced by blood flow, hypoxic signaling, and metabolic stress begins to take effect. Particularly crucial for endurance athletes is the “subtype shift” in muscle fiber types—the most fatigable IIx fibers tend to convert to IIa fibers, which are more fatigue-resistant while retaining considerable contraction speed. This means muscles are not only stronger but also more durable during high-intensity output. Additionally, sarcomere arrangement within muscle, muscle fascicle pennation angle, and tendon-muscle force transmission efficiency all change, allowing the same metabolic investment to yield higher mechanical output.

**Level 3: Tendon and elastic energy. ** Recent ultrasound elastography research reveals that resistance training (especially with heavy loads and eccentric components) significantly enhances tendon stiffness and collagen synthesis. Stiffer tendons can store and return elastic energy more efficiently during push-off or pedaling, reducing the metabolic burden of active muscle contraction—a key anatomical basis for improved exercise economy.

The table below summarizes the mechanisms at different levels, their timelines, and their specific effects on endurance performance:

Mechanism Level	Primary Changes	Typical Timeline	Effect on Endurance Performance
Neural adaptation	Motor unit recruitment↑, firing rate↑, co-contraction↓	Training weeks 1–6	RFD improved, higher output at same muscle mass
Muscle fiber adaptation	IIx→IIa conversion, cross-sectional area adjustment	Training weeks 4–12	Fatigue resistance↑, contraction efficiency↑
Tendon adaptation	Collagen synthesis↑, stiffness↑, elastic recoil↑	After training week 8	Exercise economy↑, metabolic cost↓
Metabolic/molecular adaptation	mTORC1 and AMPK signaling competition and regulation	Hours after each session	Balance between protein synthesis and mitochondrial biogenesis

It is worth emphasizing that these mechanisms are not isolated from one another but follow a relay relationship along a timeline: first, neural adaptations provide “immediate” strength gains, then structural remodeling of muscle and tendon delivers “lasting” efficiency dividends. Understanding this timeline helps athletes remain patient with the early-training phenomenon of “just getting stronger, not bigger,” and avoid giving up before reaping the long-term dividends.

Training Dosage and Dose-Response Relationship

Having confirmed that it “works,” the next key question is “how much to do.” Dose-response research tells us that the benefits of the role of serotonin and dopamine in muscle fatigue are not a linear “more is better” relationship, but rather have a minimum effective dose and a point of diminishing returns.

In terms of intensity, most studies on endurance athletes favor a heavy-load (≥80% 1RM), low-repetition (4–8 reps) “maximal strength” approach, because this pattern maximizes neural adaptation and tendon stiffness while keeping muscle hypertrophy (and the associated weight gain) to a minimum. Research by Hawley et al. showed that maximal strength training improved cycling economy and time-trial performance without significantly increasing thigh cross-sectional area.

In terms of volume, accumulating 6–10 sets per major movement per week, with 2–3 training sessions per week, is considered by most meta-analyses to be the sweet spot balancing benefit and recovery. The table below presents a typical dose-response relationship:

Dosage Range	Recommended Configuration	Applicable Period	Expected Benefit	Interference/Fatigue Risk
Minimum effective dose	1 session/week, 2–3 sets per movement	Maintenance phase, in-season	Small	Low
Standard effective dose	2 sessions/week, 3–4 sets per movement	Base phase, development phase	Medium–large	Medium
High dose	3 sessions/week, 4–6 sets per movement	Off-season strength specialization phase	Large (but diminishing returns)	High (increased interference risk)

Individual differences play a major role here. Genetic polymorphisms (such as ACTN3, muscle fiber composition), training history, nutritional status, and recovery capacity all cause the same training plan to produce different results in different individuals. The common “responder vs. low-responder” phenomenon in research reminds us that dosage must be individualized and continuously monitored with objective indicators (such as 1RM progress, RFD, time-trial performance). A practical principle is: establish a foothold at the minimum effective dose, then progressively increase with progressive overload, and decisively step back when signs of poor recovery or stagnation in endurance performance appear.

Especially in the context of concurrent training, the “ceiling” of dosage is often determined not by strength adaptation but by the degree to which it competes with endurance training for recovery resources. This is why elite endurance athletes typically use more conservative strength training doses than pure strength athletes—they seek “sufficient” strength stimulus, not “maximal” strength stimulus.

Differences Across Populations

The benefits of the role of serotonin and dopamine in muscle fatigue are not “one-size-fits-all”; population characteristics significantly modulate the direction and magnitude of adaptation.

**Beginners vs. advanced athletes. ** For novices to strength training, the rapid early progress comes almost entirely from neural adaptation, with benefits that are significant and easily obtained (the so-called “beginner gains”). However, for advanced athletes with years of training experience, the neural system’s “ceiling” is lower, and continued progress often requires more refined periodization, higher intensity, or novel stimuli (such as eccentric overload or power-oriented approaches). Research shows that effect sizes for advanced athletes are typically smaller than for beginners, but because their performance is already near personal limits, even a 1–2% improvement can be decisive in competition.

**Sex differences. ** The research by Vikmoen et al. on female road cyclists is particularly important because early literature focused mainly on males. Results show that women also achieve improvements in exercise economy and time-trial performance from strength training, and because women’s relative muscle mass starts from a lower baseline, some studies even observe greater relative room for improvement. Differences in hormonal environment (testosterone) between men and women primarily affect the absolute magnitude of muscle hypertrophy, not the “direction” of neural and tendon adaptations.

**Age differences. ** With advancing age, the loss of fast-twitch muscle fibers and motor units (sarcopenia) turns strength training from “icing on the cake” into “indispensable.” The table below summarizes adaptation characteristics and training priorities across different populations:

Population	Adaptation Characteristics	Training Priorities
Beginners	Neural adaptation dominant, rapid progress	Build movement quality, progressive loading
Advanced athletes	Slower adaptation, need refined stimuli	Periodization, power/eccentric orientation
Female athletes	Greater relative room for improvement	Same principles as males, avoid over-conservatism
Older athletes (>50)	Counteract sarcopenia, neural loss	Maintain high-intensity stimulus, emphasize RFD
Adolescents	Prioritize movement technique and safety	Start with bodyweight, avoid early heavy loads

Understanding these differences allows athletes and coaches to avoid forcing a single training plan onto everyone and to make reasonable adjustments based on individual stage and conditions. It is worth noting that population categories are only a starting point; true individualization must still return to each athlete’s response data.

Practical Training Application

Translating research into a training plan requires answering four questions: which exercises to do, at what intensity, when to schedule them, and how to monitor.

**Exercise selection. ** For cycling and running, the most transferable exercises are multi-joint, closed-chain movements that cover the hip-knee-ankle extension chain—squats, deadlifts, single-leg squats, step-ups, and calf raises. For specific goals related to the role of serotonin and dopamine in muscle fatigue, corresponding accessory exercises can be added (such as eccentric components, plyometric jumps, or core stability training).

**Intensity and sets. ** When maximal strength is the primary goal, a 4–6RM with 3–4 sets per movement and rest intervals of 3 minutes or more to ensure quality is recommended. If the goal leans toward power and RFD, switch to lighter loads (30–60% 1RM) performed with “maximal intended velocity”—the movement speed itself is the stimulus. Below is an example weekly schedule for the off-season:

Day	Main Training	Strength Session Example
Monday	Endurance (long-distance aerobic)	—
Tuesday	Strength (maximal strength orientation)	Squat 5×5, Romanian deadlift 4×6, calf raise 3×8
Wednesday	Endurance (tempo/threshold)	—
Thursday	Strength (power orientation)	Jump squat 5×3, single-leg step-up 3×6, core circuit
Friday	Recovery/technique	—
Saturday	Long endurance or race simulation	—
Sunday	Complete rest	—

**Timing and sequencing. ** To reduce interference effects, if both types of training are performed on the same day, it is recommended to separate strength and high-intensity endurance sessions by at least 6 hours, or place them on different days; when they must be done on the same day, prioritize the “capacity to be developed first” (often strength in the early season, endurance in-season).

**Monitoring indicators. ** Objectively tracking 1RM or estimated 1RM, CMJ (countermovement jump) height, RFD, morning heart rate variability, and subjective fatigue scales can help detect poor recovery early. When CMJ declines consecutively or time-trial performance stagnates, treat it as a signal to adjust dosage. Remember: strength training is the “auxiliary engine” for endurance performance—its purpose is to make you more efficient on the racecourse, not to lift heavier in the gym. Keeping this hierarchy clear prevents strength training from taking over and eroding the recovery resources of endurance training.

Local Application in Taiwan

Taiwan’s climate, terrain, and race culture bring several unique considerations to the application of the role of serotonin and dopamine in muscle fatigue.

**Recovery management in hot, humid conditions. ** Taiwan’s summer heat and humidity can impede recovery after strength training due to dehydration and reduced sleep quality. It is recommended to schedule heavy lifting in the early morning or in an air-conditioned indoor gym, and to pay particular attention to post-training hydration, electrolytes, and protein intake, avoiding stacking high-intensity endurance and strength stimuli on hot afternoons to prevent exacerbating interference effects.

**Specific demands of climbing races. ** Classic Taiwanese events such as Wuling (west approach), North-to-Wuling, and the Yangmingshan routes (Fengguizui, Balaka) are known for long-distance, high-elevation-gain profiles. These events place extremely high demands on “sustained output at low cadence and high torque,” a scenario where maximal strength and single-leg strength training transfer directly. For challenges like Wuling with its elevation changes of up to three thousand meters, maximal strength reserves in the lower limbs allow riders to maintain pedaling margin on the later steep sections, avoiding the dreaded “legs giving out first.”

**Local training resources and seasonal rhythm. ** Gyms are widely available in most Taiwanese counties and cities, allowing cyclists to use the free weights area for squats and deadlifts; those training at home can achieve similar stimuli with kettlebells, resistance bands, and bodyweight single-leg movements. For cyclists whose main training grounds are Yangmingshan, Beiyi, and the Central Cross-Island Highway, it is recommended to concentrate a strength specialization block during the off-season (typically the hottest summer period, unsuitable for long outdoor sessions), turning the hot season into a golden window for building a strength base, then returning outdoors in the cool autumn and winter to convert that strength into actual riding performance. In this way, Taiwan’s unique seasonal rhythm can perfectly align with strength training periodization, becoming a strategic advantage for local athletes.

Common Myth-Busting

Many claims circulating about the role of serotonin and dopamine in muscle fatigue do not align with academic evidence. The following clarifies them one by one.

Myth 1: “Lifting weights makes you bulky and heavy, hurting endurance.” Evidence shows that maximal-strength-oriented training (high intensity, low volume) primarily produces neural and tendon adaptations, with limited increases in muscle cross-sectional area. In most studies, body weight does not change significantly; instead, performance improves due to enhanced efficiency.

Myth 2: “Endurance athletes should only do high-repetition, light-weight ‘muscular endurance’ training.” The opposite is true: high-repetition, light-weight training provides insufficient stimulus for neural drive and tendon stiffness, and many studies indicate that heavy-load, low-repetition training has better transfer benefits.

Myth 3: “Strength training effects will show up immediately in performance.” Although neural adaptations are fast, tendon remodeling and muscle fiber conversion take weeks to months; giving up too early is a common mistake.

Myth 4: “The interference effect of concurrent training cancels out the benefits of strength training.” The interference effect does exist, but its magnitude depends heavily on training order, spacing, and dosage; with proper arrangement, strength and endurance can coexist and thrive together. Dispelling these myths allows athletes to approach training with correct expectations and invest limited time and energy where it truly pays off.

Conclusion

Looking across the evidence reviewed in this article, the role of serotonin and dopamine in muscle fatigue is no longer a question of “whether to do it,” but “how to do it smarter.” From immediate neuromuscular adaptations, to long-term remodeling of muscle fibers and tendons, to comprehensive improvements in exercise economy, multi-level mechanisms jointly support one conclusion: appropriate resistance training is an indispensable component of the endurance athlete’s toolkit.

Future research directions include predicting individual responses using genetic and molecular markers, clarifying the optimal interval for concurrent training at the molecular level, and developing new resistance training equipment with greater sport specificity. For Taiwanese cyclists and runners, the most practical course of action is: build a solid maximal strength foundation in the off-season, maintain it with the minimum effective dose in-season, and monitor throughout with objective indicators, so that strength truly translates into speed and endurance on the racecourse. Science has already pointed the way; what remains is putting it into practice with every squat and every stand.

Related Reading

• Tendon Stiffness Training and Energy Storage: Resistance Training Foundations for the Running Spring Model
• Neural Drive Improvements from Strength Training: A Temporal Analysis of EMG Studies
• The Interference Effect of Concurrent Training: Molecular Mechanisms of Conflict Between Resistance and Endurance Training
• The Impact of Muscle Coordination Training on Cycling Efficiency: Neural Control Research in Multi-Joint Movements