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Type: Journal article
Title: The effect of long-term repeated exposure to 3,4-methylenedioxymethamphetamine on cardiovascular and thermoregulatory changes
Author: Jaehne, E.
Salem, A.
Irvine, R.
Citation: Psychopharmacology, 2008; 201(2):161-170
Publisher: Springer
Issue Date: 2008
ISSN: 0033-3158
Statement of
Emily Joy Jaehne, Abdallah Salem, Rodney James Irvine
Abstract: 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.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).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.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.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.
Keywords: MDMA; Ecstasy; Thermoregulation; Behavior; Cardiovascular; Neurotransmitter
RMID: 0020083433
DOI: 10.1007/s00213-008-1258-9
Appears in Collections:Pharmacology publications

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