What is the main neurotransmitter affected by drinking caffeine, dopamine or cortisol?

Caffeine's Primary Effect on Neurotransmitters: Adenosine Antagonism Leading to Dopamine Receptor Availability

Caffeine primarily affects the brain by antagonizing adenosine receptors, which leads to increased dopamine D2/D3 receptor availability rather than directly increasing dopamine release. 1

Primary Mechanism of Action

• Caffeine is a non-selective adenosine receptor antagonist that mainly targets adenosine A1 and A2A receptors in the brain 2
• This antagonism leads to:
  • Increased availability of dopamine D2/D3 receptors in the putamen and ventral striatum 1
  • Release of pre- and postsynaptic "brakes" that adenosine normally imposes on the dopaminergic system 2
  • Enhanced alertness through blockade of adenosine's sleep-promoting effects 2

Effects on Dopaminergic System

• Caffeine increases the availability of D2/D3 receptors in the striatum rather than directly increasing dopamine release 1
• This receptor upregulation (or changes in receptor affinity) is associated with increased alertness 1
• Caffeine induces both glutamate-dependent and glutamate-independent release of dopamine by targeting:
  • A1-A2A receptor heteromers in striatal glutamatergic terminals
  • A1 receptors in striatal dopaminergic terminals 2

Effects on Cortisol

• Caffeine does elevate cortisol secretion, but this is a secondary effect rather than its primary mechanism of action 3
• Cortisol elevation occurs through:
  • CNS stimulation in men
  • Interaction with peripheral metabolic mechanisms in women 3
• Caffeine can act synergistically with mental stress to further increase cortisol levels 3

Clinical Relevance

• The increased dopamine receptor availability explains caffeine's psychostimulant effects:
  • Motor activation
  • Reinforcing properties
  • Arousal enhancement 2
• The recommended daily caffeine intake limits are:
  • Healthy adults: up to 400 mg
  • Pregnant women: 200 mg
  • Children and adolescents: <2.5 mg/kg body weight 4

Important Distinctions

• While caffeine components like N-methylpyridinium, pyrogallol, and 5-hydroxytryptamides can stimulate dopamine release in cell studies 5, the primary mechanism in the human brain involves adenosine receptor antagonism leading to increased dopamine receptor availability 1
• Caffeine's effects differ from direct dopamine-releasing stimulants, as it works primarily through the adenosine system to modulate dopaminergic function 2

In conclusion, while caffeine affects both dopaminergic signaling and cortisol levels, its primary neurochemical mechanism is adenosine receptor antagonism that increases dopamine receptor availability rather than directly increasing dopamine release or primarily acting through cortisol pathways.