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POTENTIATION OF 3,4‐METHYLENEDIOXYMETHAMPHETAMINE‐INDUCED 5‐HT RELEASE IN THE RAT SUBSTANTIA NIGRA BY CLORGYLINE, A MONOAMINE OXIDASE A INHIBITOR
Author(s) -
Hewton Ryan,
Salem Abdallah,
Irvine Rodney J
Publication year - 2007
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04734.x
Subject(s) - clorgyline , mdma , chemistry , monoamine oxidase , pharmacology , microdialysis , serotonin , extracellular , monoamine oxidase b , monoamine neurotransmitter , catecholamine , substantia nigra , dopamine , endocrinology , biochemistry , medicine , enzyme , dopaminergic , receptor
SUMMARY1 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.