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Comparative Effects of Substituted Amphetamines (PMA, MDMA, and METH) on Monoamines in Rat Caudate

B. Gough, Syed Z. Imam, Bruce E. Blough, William Slikker, Syed F. Ali

Annals of the New York Academy of Sciences June 1, 2002 DOI: 10.1111/j.1749-6632.2002.tb04182.x (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Experimental study Peer reviewed
Population Rats
Interventions PMA MDMA METH
Dose 2.5, 5, 10, 20 mg/kg (PMA); 10 and 20 mg/kg (MDMA); 2.5 mg/kg (METH)
Duration 4 hours
Topics MDMA Serotonin
Keywords Homovanillic acid Microdialysis Dopamine Meth- Monoamine neurotransmitter Extracellular Neurotoxicity Pharmacology 3,4-dihydroxyphenylacetic acid Endocrinology
Citations 47
Key findings PMA, like MDMA and METH, is capable of producing dopaminergic and serotonergic neurotoxicity in rats.

Abstract

A bstract : Paramethoxyamphetamine (PMA) is a methoxylated phenethylamine derivative that has been used illicitly in Australia since 1994. PMA is also becoming popular at rave parties in the United States. PMA raised concern when a series of fatalities resulted after its use in South Australia, where it was marketed as “ecstasy,” which is the colloquial name for MDMA. In the present study, we evaluated the comparative neurotoxicity of substituted amphetamines in rats. Extracellular levels of dopamine (DA), 3,4‐dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5‐HT), and 5‐hydroxyindoleacetic acid (5‐HIAA) were assayed in the caudate of freely moving rats using microdialysis and HPLC‐EC. Dialysates were assayed every 20 minutes for 4 hours after an intraperitoneal (i.p.) injection of PMA (2.5, 5, 10, 20 mg/kg), MDMA (10 and 20 mg/kg), or METH (2.5 mg/kg). METH produced a significant increase in extracellular DA (700%), and significant decreases in extracellular DOPAC and HVA (30% and 50%), with no detectable changes in either 5‐HT or 5‐HIAA. MDMA produced significant increases in DA (700% at 10 mg/kg and 950% at 20 mg/kg) and decreases in DOPAC (15% for both 10 and 20 mg/kg), and HVA (50% at 10 mg/kg and 35% at 20 mg/kg). MDMA also increased 5‐HT (350% at 10, and 575% at 20 mg/kg), and decreased 5‐HIAA to 60% for both dose levels. PMA produced no detectable increases in DA at dose levels of 2.5, 5, or 10 mg/kg, but significantly increased DA (975%) at a dose of 20 mg/kg. However, PMA significantly decreased DOPAC at all dose levels (75% at 2.5; 40% at 5; 30% at 10; 10% at 20 mg/kg), with comparable decreases in HVA at all dose levels. PMA also produced significant increases in 5‐HT at 10 and 20 mg/kg (350% for both dose levels), with no detectable changes in 5‐HT at 2.5 or 5 mg/kg. All dose levels of PMA significantly decreased 5‐HIAA (50 to 70%). These data suggest that PMA, like MDMA and METH, is capable of producing dopaminergic and serotonergic neurotoxicity.

Comparable studies

Other preclinical and animal studies on MDMA, most cited first.

Study Year Design Participants
Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) 1987 Experimental study
3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain 1987 Animal experiment
Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells 2006 In vitro laboratory study
Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Rats 1998 Experimental study
Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Squirrel monkeys treated with MDMA 1999 Observational cohort

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MDMA Serotonin