MDMA self-administration fails to alter the behavioral response to 5-HT(1A) and 5-HT(1B) agonists.

Dane Aronsen; Susan Schenk

doi:10.1007/s00213-016-4226-9

MDMA self-administration fails to alter the behavioral response to 5-HT(1A) and 5-HT(1B) agonists.

Dane Aronsen, Susan Schenk

Psychopharmacology April 2016 DOI: 10.1007/s00213-016-4226-9 (opens in new tab)

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Study at a glance

AI-extracted from the abstract

Characteristics	Observational cohort Peer reviewed
Population	Male Sprague-Dawley rats
Interventions	MDMA 8-OH-DPAT RU 24969
Dose	MDMA 350 mg/kg total; 8-OH-DPAT 0.03-1.0 mg/kg; RU 24969 0.3-3.0 mg/kg
Duration	20-58 daily self-administration sessions; assessed 2 days after the last session
Topics	MDMA Serotonin
Keywords	5-ht1a 5-ht1b 8-oh-dpat Ru 24969 Self-administration
Key findings	MDMA self-administration did not alter the dose-dependent hyperactivity produced by the 5-HT1A agonist 8-OH-DPAT or the adipsic response to the 5-HT1B/1A agonist RU 24969. The authors conclude that behavioral deficits from repeated MDMA exposure are unlikely to involve 5-HT1A or 5-HT1B receptor mechanisms.

Abstract

Regular use of the street drug, ecstasy, produces a number of cognitive and behavioral deficits. One possible mechanism for these deficits is functional changes in serotonin (5-HT) receptors as a consequence of prolonged 3,4 methylenedioxymethamphetamine (MDMA)-produced 5-HT release. Of particular interest are the 5-HT(1A) and 5-HT(1B) receptor subtypes since they have been implicated in several of the behaviors that have been shown to be impacted in ecstasy users and in animals exposed to MDMA. This study aimed to determine the effect of extensive MDMA self-administration on behavioral responses to the 5-HT(1A) agonist, 8-hydroxy-2-(n-dipropylamino)tetralin (8-OH-DPAT), and the 5-HT(1B/1A) agonist, RU 24969. Male Sprague-Dawley rats self-administered a total of 350 mg/kg MDMA, or vehicle, over 20-58 daily self-administration sessions. Two days after the last self-administration session, the hyperactive response to 8-OH-DPAT (0.03-1.0 mg/kg) or the adipsic response to RU 24969 (0.3-3.0 mg/kg) were assessed. 8-OH-DPAT dose dependently increased horizontal activity, but this response was not altered by MDMA self-administration. The dose-response curve for RU 24969-produced adipsia was also not altered by MDMA self-administration. Cognitive and behavioral deficits produced by repeated exposure to MDMA self-administration are not likely due to alterations in 5-HT(1A) or 5-HT(1B) receptor mechanisms.

Comparable studies

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

Study	Year	Design
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

Citations in the library

Cited by 1

Methylenedioxymethamphetamine (MDMA): Serotonergic and dopaminergic mechanisms related to its use and misuse Journal of Neurochemistry March 12, 2021

Cites 16

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