POTENTIATION OF 3,4-METHYLENEDIOXYMETHAMPHETAMINE-INDUCED 5-HT RELEASE IN THE RAT SUBSTANTIA NIGRA BY CLORGYLINE, A MONOAMINE OXIDASE A INHIBITOR

Authors: Hewton, Ryan; Salem, Abdallah; Irvine, Rodney J

Source: Clinical and Experimental Pharmacology and Physiology, Volume 34, Number 10, October 2007 , pp. 1051-1057(7)

Publisher: Wiley-Blackwell

Abstract:

SUMMARY

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It is well established that the commonly used recreational drugs 3,4-methylenedioxymethamphetamine (MDMA, `ecstasy') and para-methoxyamphetamine (PMA) facilitate the release and prevent the reuptake of 5-hydroxytryptamine (5-HT, serotonin). Although these drugs have similar potencies for their abilities to increase the release and inhibit the re-uptake of 5-HT, PMA has greater potency as an inhibitor of monoamine oxidase (MAO)-A.

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The present study compared the abilities of PMA and MDMA to increase extracellular 5-HT concentrations in animals with functional MAO-A and when MAO-A activity was inhibited by clorgyline.

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Samples of extracellular fluid from rat substantia nigra were collected using microdialysis and then analysed for 5-HT and 5-hydroxyindol acetic acid (5-HIAA) by high-performance liquid chromatography coupled with electrochemical detection. The 5-HT-mediated effects on body temperature and behaviour were also recorded. Rats were pretreated with saline or 10 mg/kg, i.p., clorgyline and, 24 h later, injected with 10 mg/kg MDMA, PMA or saline.

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Both MDMA and PMA produced significant increases in extracellular 5-HT concentrations (482 ± 83 and 726 ± 287%, respectively; P < 0.05). Rats treated with PMA and MDMA displayed significantly increased 5-HT-related behavours (P < 0.05). Furthermore, only MDMA was capable of producing additional significant increases in 5-HT concentrations (1033 ± 131%; P < 0.01) when coadministered with clorgyline.

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The results of the present study suggest that PMA and MDMA are similar in their abilities to increase extracellular 5-HT levels in animals with functional MAO-A activity. However, coadministration of these substituted amphetamines with an MAO-A inhibitor causes significant potentiation in the ability to increase extracellular levels of 5-HT for MDMA, but not PMA.

Keywords: clorgyline; ecstasy; hyperthermia; 3,4-methylenedioxymethamphetamine; monoamine oxidase-A inhibitor; para-methoxyamphetamine

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1440-1681.2007.04734.x

Publication date: 2007-10-01

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