What neurotransmitters are released during exercise?

Neurotransmitters Released During Exercise

Exercise stimulates the release of several key neurotransmitters including catecholamines (norepinephrine and epinephrine), serotonin, dopamine, acetylcholine, and endorphins, which contribute to both physical and mental health benefits.

Primary Neurotransmitters Released During Exercise

Catecholamines

• Norepinephrine and epinephrine (adrenaline) are significantly released during exercise 1
• Studies show that exercise training can lead to a 19% drop in resting epinephrine levels after a 3-month program 1
• Catecholamine release varies based on exercise intensity and duration, with higher levels observed in trained individuals (the "sports adrenal medulla" effect) 1

Serotonin (5-HT)

• Exercise increases serotonin release in the brain through the 5-HT3-IGF-1 mechanism 2
• Swimming exercise specifically increases sensitivity of serotonin 5-HT2 receptors and postsynaptic 5-HT1A receptors 2
• The tryptophan to large neutral amino acids (TRP/LNAA) ratio increases after exercise, enhancing serotonin production 2

Dopamine

• Exercise increases dopamine release and dopamine receptor expression (D1R and D2R) 2
• Voluntary wheel running in animal studies stimulates activity in serotonin neurons but not directly in dopamine neurons 3
• Dopaminergic transmission improvements may reciprocally increase motivation to exercise 4

Endorphins and Other Opioid Peptides

• Both anaerobic and aerobic exercises increase beta-endorphin, enkephalin, and dynorphin levels 2
• These endogenous opioids contribute to the mood-elevating effects of exercise

GABA and Glutamate

• Exercise leads to significant increases in GABAAR (γ2 and α2 subunits) 2
• Exercise increases glutamate and PGC1α while reducing glutamatergic neurotoxicity 2

Acetylcholine

• Exercise increases expression of muscarinic M5 receptors and nicotinic α7 receptors 2
• This leads to significant increases in acetylcholine release

Physiological Mechanisms and Effects

Cardiovascular and Respiratory Effects

• Exercise-induced catecholamine release helps regulate blood flow distribution, with up to 80% of cardiac output redirected to working muscles during intense exercise 1
• This redistribution can lead to splanchnic hypoperfusion (reduced gut blood flow) during strenuous exercise 1

Central Nervous System Effects

• Exercise-induced neurotransmitter release contributes to improved mood and reduced anxiety 5, 6
• Physical activity has been shown to reduce depression symptoms through monoaminergic mechanisms 2, 4
• Enhanced vagal control of heart rate variability, with a shift away from sympathetic dominance, has been documented after 8 weeks of home training 1

Regulatory T Cell Function

• Exercise affects regulatory T cell function through catecholaminergic signaling 1
• β2-adrenergic receptor stimulation by exercise-induced catecholamines increases intracellular cAMP levels in regulatory T cells 1

Clinical Implications

Mental Health Benefits

• The antidepressant effects of exercise are mediated at least partly through activation of serotonin neurons 3
• Exercise can potentiate the response to SSRIs by increasing basal firing activity of serotonin neurons 3
• Physical activity can be used to reduce depression by affecting neurotransmitters, neuromodulators, cytokines, and neurotrophins 2

Exercise Prescription Considerations

• Moderate to high-intensity exercise appears most effective for neurotransmitter release
• Both aerobic and anaerobic exercises stimulate beneficial neurotransmitter changes 2
• Exercise intensity and duration should be considered when targeting specific neurotransmitter systems

Common Pitfalls and Caveats

• Individual variability exists in neurotransmitter response to exercise based on fitness level, age, and health status
• Excessive high-intensity exercise may lead to adverse effects through extreme catecholamine release and splanchnic hypoperfusion 1
• The relationship between exercise intensity and neurotransmitter release is not linear for all systems
• Measurement of neurotransmitter changes in humans is challenging, with many studies relying on animal models 3

Understanding these neurotransmitter responses to exercise provides insight into the physiological mechanisms behind exercise's beneficial effects on both physical and mental health.