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https://hdl.handle.net/2440/51775
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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 1432-2072 |
Statement of Responsibility: | Emily Joy Jaehne, Abdallah Salem, Rodney James Irvine |
Abstract: | <h4>Rationale</h4>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.<h4>Objectives</h4>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).<h4>Materials and methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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 |
DOI: | 10.1007/s00213-008-1258-9 |
Published version: | http://dx.doi.org/10.1007/s00213-008-1258-9 |
Appears in Collections: | Aurora harvest Pharmacology publications |
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