Caffeine promotes dopamine D1 receptor-mediated body temperature, heart rate and behavioural responses to MDMA ('ecstasy')

Psychopharmacology (Berl). 2010 Jul;211(1):15-25. doi: 10.1007/s00213-010-1864-1. Epub 2010 May 2.


Rationale: Caffeine exacerbates the acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') in rats characterised by hyperthermia, tachycardia and lethality. Depletion of central catecholamine stores and dopamine D(1) receptor blockade have been reported to attenuate the ability of caffeine to exacerbate MDMA-induced hyperthermia.

Objectives: Here, we investigate whether dopamine D(1) and D(2) receptors mediate the effects of caffeine on MDMA-induced changes in body temperature, heart rate and locomotor activity.

Methods: All parameters were recorded continuously in individually housed rats using bioradiotelemetry from 1 h prior to 4 h following caffeine (10 mg/kg, s.c.) and/or MDMA (10 mg/kg, s.c.) administration.

Results: Co-administration of caffeine with MDMA provoked a switch from MDMA-induced hypothermia and bradycardia to hyperthermia and tachycardia without influencing MDMA-induced hyperlocomotion. Pre-treatment with a specific dopamine D(1/5) antagonist SCH 23390 (1 mg/kg) enhanced MDMA-induced hypothermia and blocked the ability of caffeine to provoke a switch from MDMA-induced hypothermia to hyperthermia. Furthermore, SCH 23390 blocked MDMA-induced hyperactivity and the ability of caffeine to promote a tachycardic response to MDMA. By contrast, pre-treatment with the selective D(2) antagonist, sulpiride (100 mg/kg) blocked MDMA-induced hypothermia, failed to influence the ability of caffeine to promote tachycardia whilst enhancing MDMA-induced hyperactivity.

Conclusions: Our results highlight the importance of dopamine D(1) and D(2) receptors in shaping the behavioural and physiological response to MDMA and suggest that the ability of caffeine to provoke MDMA-induced toxicity is associated with the promotion of dopamine D(1) over D(2) receptor-related responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects*
  • Benzazepines / pharmacology
  • Body Weight / drug effects*
  • Caffeine / pharmacology*
  • Central Nervous System Stimulants / pharmacology*
  • Dopamine Agents / pharmacology
  • Drug Interactions
  • Hallucinogens / adverse effects
  • Heart Rate / drug effects*
  • Locomotion / drug effects
  • Male
  • N-Methyl-3,4-methylenedioxyamphetamine / adverse effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D1 / metabolism*
  • Sulpiride / pharmacology
  • Time Factors


  • Benzazepines
  • Central Nervous System Stimulants
  • Dopamine Agents
  • Hallucinogens
  • Receptors, Dopamine D1
  • SCH 23390
  • Caffeine
  • Sulpiride
  • N-Methyl-3,4-methylenedioxyamphetamine