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

Abstract

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 D1 receptor blockade have been reported to attenuate the ability of caffeine to exacerbate MDMA-induced hyperthermia.

Objectives

Here, we investigate whether dopamine D1 and D2 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 D1/5 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 D2 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 D1 and D2 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 D1 over D2 receptor-related responses.

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Acknowledgements

The authors gratefully acknowledge the support from the Health Research Board of Ireland. The authors would also like to thank NIDA (USA) for the generous gift of MDMA.

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Correspondence to Andrew Harkin.

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Vanattou-Saïfoudine, N., McNamara, R. & Harkin, A. Caffeine promotes dopamine D1 receptor-mediated body temperature, heart rate and behavioural responses to MDMA (‘ecstasy’). Psychopharmacology 211, 15–25 (2010). https://doi.org/10.1007/s00213-010-1864-1

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  • DOI: https://doi.org/10.1007/s00213-010-1864-1

Keywords

  • MDMA
  • Caffeine
  • Body temperature
  • Heart rate
  • Locomotor activity
  • Dopamine receptors
  • Rat