What are the effects of serotonin, norepinephrine (NE), and dopamine on the body?

Effects of Serotonin, Norepinephrine, and Dopamine on the Body

Serotonin, norepinephrine, and dopamine have distinct physiological effects on multiple organ systems, with dopamine producing dose-dependent effects through different receptor activations, norepinephrine primarily affecting cardiovascular function, and serotonin influencing mood regulation. 1, 2

Dopamine Effects

Dose-Dependent Receptor Activation

• Low doses (1-5 μg/kg/min): Primarily activates dopaminergic receptors

  • Increases renal blood flow and glomerular filtration rate
  • Enhances sodium excretion and urine output
  • Improves mesenteric blood flow with minimal effect on blood pressure 2

• Moderate doses (5-10 μg/kg/min): Activates β-adrenergic receptors

  • Increases myocardial contractility and heart rate
  • Increases cardiac output
  • Modestly increases systolic blood pressure 2

• High doses (>10 μg/kg/min): Activates α-adrenergic receptors

  • Causes peripheral vasoconstriction
  • Increases systemic vascular resistance
  • Significantly increases blood pressure
  • May decrease renal blood flow 2

Hormonal and Metabolic Effects

• Decreases serum concentrations of anterior pituitary hormones (prolactin, thyrotrophic releasing hormone, growth hormone, and luteinizing hormone)
• Can induce or aggravate low-T syndrome by suppressing thyroid stimulating hormone
• Decreases thyroxin and tri-iodo-thyroxin levels
• Suppresses serum dehydroepiandrosterone sulphate
• Blunts pulsatile growth hormone secretion 1

Immune Effects

• May aggravate sepsis-associated immune paralysis
• Decreases serum levels of prolactin, triggering T cell hyporesponsiveness
• May reduce lymphocyte count
• Can inhibit transformation of lymphocytes by mitogens 1

Norepinephrine Effects

Cardiovascular Effects

• Increases blood pressure primarily through vasoconstriction
• Has variable effects on cardiac output depending on baseline cardiovascular state
• Increases stroke volume and coronary blood flow via β2-receptor stimulation
• Causes less tachycardia than dopamine due to vagal reflex activity from increased blood pressure 1, 2

Immune Effects

• May downregulate endotoxin-induced release of proinflammatory cytokines
• Upregulates anti-inflammatory cytokines (e.g., IL-10)
• May stimulate bacterial growth by removing iron from lactoferrin and transferrin 1

Metabolic Effects

• Stimulation of α-adrenergic receptors inhibits insulin release from pancreatic β cells
• Activates glycogenolysis and lactate production in skeletal muscles 1

Serotonin Effects

Mood Regulation

• Serotonin depletion studies show that reduced serotonin levels do not decrease mood in healthy individuals without predisposition to depression
• However, serotonin depletion can lower mood in individuals with family history of major depressive disorder
• Can induce relapse in patients with major depressive disorder in remission who use serotonergic antidepressants 3

Interaction with Dopaminergic Systems

• Serotonin modulates dopaminergic neuron activity in a state-dependent and region-dependent manner
• Generally exerts phasic and excitatory control over dopamine neurons
• 5-HT2C receptors provide tonic and/or constitutively inhibitory control of dopamine neurons 4

Interaction with Norepinephrine

• Serotonergic projections have an inhibitory effect on norepinephrine neurons
• This interaction has implications for the treatment of depression and anxiety disorders 5

Neurotransmitter Interactions

• Fluoxetine (a selective serotonin reuptake inhibitor) uniquely increases not only serotonin but also norepinephrine and dopamine levels in the prefrontal cortex, unlike other SSRIs 6

• Methylphenidate increases extracellular dopamine and norepinephrine but has no effect on serotonin levels, in contrast to amphetamine which increases all three neurotransmitters 7

• Complex behavioral patterns reflect interactions among these neurotransmitters rather than isolated effects 5

Clinical Implications

• Dopamine is more arrhythmogenic than norepinephrine, with significantly higher rates of both supraventricular and ventricular arrhythmias 2

• Dopamine is associated with increased mortality risk compared to norepinephrine in septic shock 2

• Selective β1 blockade may decrease circulating inflammatory cytokines, inhibit bacterial growth, and improve fibrinolysis 1

• Understanding these neurotransmitter interactions is crucial for optimizing treatment approaches for depression, anxiety disorders, schizophrenia, Parkinson's disease, and other neuropsychiatric conditions 4, 5