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The effects of co-administration of 3,4-methylenedioxymethamphetamine ("ecstasy") or para-methoxyamphetamine and moclobemide at elevated ambient temperatures on striatal 5-HT, body temperature and behavior in rats.
Neuroscience 2007; 146(1):321-9N

Abstract

We have recently demonstrated that co-administration of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") with the reversible monoamine oxidase type A (MAO-A) inhibitor moclobemide at an ambient temperature of 22 degrees C significantly increases striatal 5-HT outflow and 5-HT-mediated behaviors. In the present study, using microdialysis, we examined the effects of co-administration of MDMA or para-methoxyamphetamine (PMA) with moclobemide on striatal 5-HT outflow at the elevated ambient temperatures of 30 degrees C. Samples were collected every 30 min for 4 h and analyzed by high-performance liquid chromatography assay with electrochemical detection (HPLC-ED). 5-HT-mediated effects on body temperature and behavior were also recorded. Rats were treated with either saline or 20 mg/kg (i.p.) moclobemide, followed by 10 mg/kg (i.p.) MDMA, 10 mg/kg (i.p.) PMA or saline 60 min later. Both MDMA and PMA produced significant increases in 5-HT outflow (370% peak and 309% peak, respectively, P<0.05). MDMA and PMA significantly increased body temperature (+2.0 degrees C and +2.1 degrees C, respectively, P<0.01) and drug-related behaviors (P<0.05). When MDMA or PMA was co-administered with moclobemide, additional significant increases were seen in 5-HT outflow (850% peak, P<0.01 and 1450% peak, P<0.001, respectively) and only MDMA showed additional significant increase in body temperature (+5.0 degrees C, P<0.001). No additional increases were seen in behavioral activity. When moclobemide was co-administered with MDMA, sustained increases in body temperature were recorded that were significantly higher than with MDMA alone and such increases were not observed in our previous study at normal room temperature. Our results suggest greater risk of MDMA-induced adverse effects on body temperature regulation, compared with PMA, when used in combination with moclobemide at elevated ambient temperatures.

Authors+Show Affiliations

Discipline of Pharmacology, School of Medical Sciences, Medical School North, University of Adelaide, Adelaide, South Australia 5005, Australia.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17306465

Citation

Stanley, N, et al. "The Effects of Co-administration of 3,4-methylenedioxymethamphetamine ("ecstasy") or Para-methoxyamphetamine and Moclobemide at Elevated Ambient Temperatures On Striatal 5-HT, Body Temperature and Behavior in Rats." Neuroscience, vol. 146, no. 1, 2007, pp. 321-9.
Stanley N, Salem A, Irvine RJ. The effects of co-administration of 3,4-methylenedioxymethamphetamine ("ecstasy") or para-methoxyamphetamine and moclobemide at elevated ambient temperatures on striatal 5-HT, body temperature and behavior in rats. Neuroscience. 2007;146(1):321-9.
Stanley, N., Salem, A., & Irvine, R. J. (2007). The effects of co-administration of 3,4-methylenedioxymethamphetamine ("ecstasy") or para-methoxyamphetamine and moclobemide at elevated ambient temperatures on striatal 5-HT, body temperature and behavior in rats. Neuroscience, 146(1), pp. 321-9.
Stanley N, Salem A, Irvine RJ. The Effects of Co-administration of 3,4-methylenedioxymethamphetamine ("ecstasy") or Para-methoxyamphetamine and Moclobemide at Elevated Ambient Temperatures On Striatal 5-HT, Body Temperature and Behavior in Rats. Neuroscience. 2007 Apr 25;146(1):321-9. PubMed PMID: 17306465.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effects of co-administration of 3,4-methylenedioxymethamphetamine ("ecstasy") or para-methoxyamphetamine and moclobemide at elevated ambient temperatures on striatal 5-HT, body temperature and behavior in rats. AU - Stanley,N, AU - Salem,A, AU - Irvine,R J, Y1 - 2007/02/15/ PY - 2006/09/18/received PY - 2006/12/18/revised PY - 2007/01/11/accepted PY - 2007/2/20/pubmed PY - 2007/7/19/medline PY - 2007/2/20/entrez SP - 321 EP - 9 JF - Neuroscience JO - Neuroscience VL - 146 IS - 1 N2 - We have recently demonstrated that co-administration of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") with the reversible monoamine oxidase type A (MAO-A) inhibitor moclobemide at an ambient temperature of 22 degrees C significantly increases striatal 5-HT outflow and 5-HT-mediated behaviors. In the present study, using microdialysis, we examined the effects of co-administration of MDMA or para-methoxyamphetamine (PMA) with moclobemide on striatal 5-HT outflow at the elevated ambient temperatures of 30 degrees C. Samples were collected every 30 min for 4 h and analyzed by high-performance liquid chromatography assay with electrochemical detection (HPLC-ED). 5-HT-mediated effects on body temperature and behavior were also recorded. Rats were treated with either saline or 20 mg/kg (i.p.) moclobemide, followed by 10 mg/kg (i.p.) MDMA, 10 mg/kg (i.p.) PMA or saline 60 min later. Both MDMA and PMA produced significant increases in 5-HT outflow (370% peak and 309% peak, respectively, P<0.05). MDMA and PMA significantly increased body temperature (+2.0 degrees C and +2.1 degrees C, respectively, P<0.01) and drug-related behaviors (P<0.05). When MDMA or PMA was co-administered with moclobemide, additional significant increases were seen in 5-HT outflow (850% peak, P<0.01 and 1450% peak, P<0.001, respectively) and only MDMA showed additional significant increase in body temperature (+5.0 degrees C, P<0.001). No additional increases were seen in behavioral activity. When moclobemide was co-administered with MDMA, sustained increases in body temperature were recorded that were significantly higher than with MDMA alone and such increases were not observed in our previous study at normal room temperature. Our results suggest greater risk of MDMA-induced adverse effects on body temperature regulation, compared with PMA, when used in combination with moclobemide at elevated ambient temperatures. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/17306465/The_effects_of_co_administration_of_34_methylenedioxymethamphetamine__"ecstasy"__or_para_methoxyamphetamine_and_moclobemide_at_elevated_ambient_temperatures_on_striatal_5_HT_body_temperature_and_behavior_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(07)00065-6 DB - PRIME DP - Unbound Medicine ER -