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Published on: January 22, 2016
The effect of long-term repeated exposure to 3,4-methylenedioxymethamphetamine on cardiovascular and thermoregulatory
Emily Joy Jaehne1, Abdallah Salem, Rodney James Irvine
1Discipline of Pharmacology, School of Medical Sciences, Level 5 Medical School North, University of Adelaide, Adelaide, SA, 5005, Australia. emily.jaehne@adelaide.edu.au
Rationale:
3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") disrupts thermoregulation in rats and can lead to life-threatening hyperthermia in humans. MDMA administration can also lead to long-term neurotoxicity in animals and possibly humans.
Objectives:
The purpose of the current study was to extend previous results on the acute effects of MDMA on behavioral thermoregulation to a repeated dosing regime, simulating regular weekend use of ecstasy, on measures of thermoregulation and heart rate (HR).
Materials And Methods:
Sprague-Dawley rats with telemetry implants were administered 40 micromol/kg MDMA on three consecutive days each week for 1 or 6 weeks before being confined to an elevated ambient temperature (TA) (HOT; 30+/-1 degrees C) or an area at room temperature (ROOM; 21.5+/-1.5 degrees C) for 30 min. After the final drug administration, rats were placed in a thermal gradient for 4 h to allow behavioral thermoregulation.
Results:
HOT rats showed higher core temperature (TC), HR, and locomotor activity than ROOM rats during confinement to a set TA (P<0.001). HR responses to MDMA over 6 weeks at both TAs progressively decreased with repeated dosing (P<0.05). TC was significantly higher in both 6-week groups compared to the 1-week groups (P<0.05) at the end of time in the gradient. Cortical concentrations of dihydroxyphenylacetic acid (DOPAC; P<0.05) and 5-hydroxyindole acetic acid (5-HIAA; P<0.001) decreased significantly irrespective of TA, while concentrations of dopamine and 5-HT did not change.
Conclusion:
Long-term treatment with MDMA resulted in apparent tolerance to the effects of the drug on HR, dysregulation of TC in thermal gradient, and depletion of cortical DOPAC and 5-HIAA.
Insights
Repeated MDMA (ecstasy) use in rats led to tolerance in heart rate responses and disrupted body temperature regulation. Long-term exposure also depleted key brain chemicals, indicating potential neurotoxicity.
Area of Science:
- Neuropharmacology
- Behavioral Neuroscience
- Toxicology
Background:
- 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is known to impair thermoregulation and cause hyperthermia in humans and rats.
- MDMA exposure may also lead to long-term neurotoxic effects in animal models and potentially humans.
Purpose of the Study:
- To investigate the effects of repeated MDMA administration on thermoregulation and heart rate (HR) in rats.
- To simulate regular "weekend use" patterns of ecstasy consumption.
Main Methods:
- Sprague-Dawley rats received daily MDMA doses for 1 or 6 weeks.
- Rats were exposed to high ambient temperature (30°C) or room temperature (21.5°C).
- Behavioral thermoregulation was assessed in a thermal gradient post-treatment.
Main Results:
- Repeated MDMA dosing led to decreased heart rate responses, suggesting tolerance development.
- Long-term MDMA treatment resulted in higher core body temperatures in the thermal gradient compared to short-term treatment.
- Cortical levels of dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5-HIAA) were significantly reduced.
Conclusions:
- Long-term MDMA exposure induces tolerance to its cardiovascular effects.
- Repeated MDMA administration dysregulates thermoregulation in a thermal gradient.
- Depletion of cortical DOPAC and 5-HIAA suggests potential long-term neurotoxic consequences of chronic MDMA use.
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