Potentiation of 3,4-methylenedioxymethamphetamine-induced 5-HT release in the rat substantia nigra by clorgyline, a monoamine oxidase a inhibitor

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dc.contributor.authorHewton, R.
dc.contributor.authorSalem, A.
dc.contributor.authorIrvine, R.
dc.date.issued2007
dc.descriptionThe definitive version is available at www.blackwell-synergy.com
dc.description.abstract1. 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. 2. 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. 3. 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. 4. 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. 5. 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.
dc.identifier.citationClinical and Experimental Pharmacology and Physiology, 2007; 34(10):1051-1057
dc.identifier.doi10.1111/j.1440-1681.2007.04734.x
dc.identifier.issn0305-1870
dc.identifier.issn1440-1681
dc.identifier.orcidSalem, A. [0000-0002-4555-9794]
dc.identifier.urihttp://hdl.handle.net/2440/41472
dc.language.isoen
dc.publisherBlackwell Publishing Asia
dc.source.urihttps://doi.org/10.1111/j.1440-1681.2007.04734.x
dc.subjectclorgyline
dc.subjectecstasy
dc.subjecthyperthermia
dc.subject3
dc.subject4-methylenedioxymethamphetamine
dc.subjectmonoamine oxidase-A inhibitor
dc.subjectpara-methoxyamphetamine
dc.titlePotentiation of 3,4-methylenedioxymethamphetamine-induced 5-HT release in the rat substantia nigra by clorgyline, a monoamine oxidase a inhibitor
dc.typeJournal article
pubs.publication-statusPublished

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