MDMA-induced impairment in primates: antagonism by a selective norepinephrine or serotonin, but not by a dopamine/norepinephrine transport inhibitor
Christopher D. Verrico, Laurie J. Lynch, Michele A. Fahey, Ashley-Kay Fryer, Gregory M. Miller, Bertha K. Madras
Journal of Psychopharmacology January 21, 2008 DOI: 10.1177/0269881107083639 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study with in vitro and in vivo components Peer reviewed |
|---|---|
| Sample size | 4 |
| Population | Cynomolgus monkeys (Macaca fascicularis) |
| Interventions | MDMA citalopram desipramine methylphenidate |
| Dose | 1.5 mg/kg |
| Duration | Once-weekly dosing, up to three days post-exposure monitoring |
| Topics | MDMA Serotonin |
| Keywords | Norepinephrine transporter Serotonin transporter Pharmacology Dopamine transporter Citalopram Monoamine neurotransmitter Serotonin reuptake inhibitor |
| Citations | 31 |
| Key findings | Oral MDMA increased error rates in a cognitive task for up to three days, and this impairment was reversed by inhibitors of the serotonin transporter and norepinephrine transporter but not by a dopamine/norepinephrine transporter inhibitor. |
Abstract
Human MDMA (R,S-3,4-methylenedioxymethamphetamine) users display selective cognitive deficits after acute MDMA exposure, frequently attributed to serotonin deficits. We postulated that MDMA will compromize executive function in primates and that an inhibitor of the serotonin transporter (SERT) and the norepinephrine transporter (NET) but not the dopamine (DAT) transporter, will prevent impairment. The potencies of DAT/NET, NET and SERT inhibitors to block transport of [ 3 H]MDMA and [ 3 H]monoamines were compared in vitro. Subsequently, cynomolgus monkeys (Macaca fasicularis) were trained to stable performance in a reversal learning task. Effects of once-weekly oral or i.m. dose of MDMA (1.5 mg/kg, n = 4) on performance were monitored, alone or after pretreatment with inhibitors of the SERT, DAT or NET (prior to i.m. MDMA). 1) Drug potencies for blocking [ 3 H]MDMA or [ 3 H]monoamine transport were not consistent; 2) Oral MDMA increased error rates in a cognitive task for up to three days following exposure, whereas intramuscular MDMA prevented subjects from performing the cognitive task on the day of administration, but not on subsequent days; 3) The SERT inhibitor citalopram and the NET inhibitor desipramine, but not the DAT/NET inhibitor methylphenidate, reversed the effects of MDMA on task performance and mandibular movements induced by i.m. MDMA and 4) MDMA altered sleep latency. Oral MDMA impairs executive function in monkeys for several days, a finding of potential relevance to MDMA consumption by humans. Reversal of impaired executive function by a NET inhibitor implicates the NET and norepinephrine in MDMA-induced cognitive impairment and may be relevant to therapeutic strategies.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 15
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- Duloxetine Inhibits Effects of MDMA (“Ecstasy") In Vitro and in Humans in a Randomized Placebo-Controlled Laboratory Study PLoS One May 4, 2012
- The Norepinephrine Transporter Inhibitor Reboxetine Reduces Stimulant Effects of MDMA (“Ecstasy”) in Humans Clinical Pharmacology & Therapeutics June 15, 2011
- Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA administered alone or in combination The International Journal of Neuropsychopharmacology October 8, 2013
- Efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for posttraumatic stress disorder: A systematic review and meta-analysis. Progress in Neuro-Psychopharmacology and Biological Psychiatry 2020
and 10 more in the library
Cites 21
- Gender differences in the subjective effects of MDMA Psychopharmacology March 5, 2001
- Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research Human Psychopharmacology: Clinical and Experimental December 1, 2001
- Mood and cognitive effects of ± 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’): week‐end ‘high’ followed by mid‐week low Addiction July 1, 1997
- Human Pharmacology of 3,4-Methylenedioxymeth-amphetamine ("Ecstasy"): Psychomotor Performance and Subjective Effects Journal of Clinical Psychopharmacology August 1, 2000
- The Psychological and Physiological Effects of MDMA on Normal Volunteers Journal of Psychoactive Drugs October 1, 1986
and 16 more in the library