Comparison of the effects of abstinence on MDMA and cocaine self-administration in rats.

Quenten Highgate; Susan Schenk

doi:10.1007/s00213-018-5026-1

Comparison of the effects of abstinence on MDMA and cocaine self-administration in rats.

Quenten Highgate, Susan Schenk

Psychopharmacology November 2018 DOI: 10.1007/s00213-018-5026-1 (opens in new tab)

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AI-extracted from the abstract

Characteristics	Randomized controlled trial Peer reviewed
Population	Rats self-administering MDMA or cocaine
Interventions	MDMA Cocaine
Dose	350 mg/kg
Duration	0- or 14-day abstinence, followed by 7 additional days of self-administration testing
Topics	MDMA Serotonin
Keywords	Abstinence Cocaine Self-administration
Key findings	Abstinence reduced subsequent MDMA self-administration but not cocaine self-administration. Cocaine was self-administered faster than MDMA, and MDMA responding was concentrated in the first hour of each session while cocaine responding was evenly distributed. The authors argue the selective reduction is consistent with MDMA-stimulated serotonin release being inhibitory to MDMA self-administration.

Abstract

3,4-Methylenedioxymethamphetamine (MDMA) preferentially increases synaptic serotonin (5HT). This response was attenuated following repeated exposure but there was recovery as a result of abstinence. Effects of abstinence on self-administration of many drugs have been documented but the impact on MDMA self-administration is unknown. This study compared the effects of abstinence on MDMA and cocaine self-administration. Six-hour daily MDMA or cocaine sessions were conducted until a total of 350 mg/kg had been self-administered. Following this, rats were randomly assigned to either a 0- or 14-day abstinence group. Self-administration testing then continued for an additional 7 days. The latency to self-administer 350 mg/kg was shorter for rats that self-administered cocaine. The temporal distribution of responding within each test session also differed; MDMA self-administration was high during the first hour of each session, and decreased during subsequent hours, whereas cocaine self-administration was evenly distributed throughout each hour of the session. Abstinence decreased MDMA but not cocaine self-administration. The selective reduction of MDMA self-administration following abstinence is consistent with the idea that MDMA-stimulated 5-HT release is inhibitory to MDMA self-administration.

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

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