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Intravenous self-administration of entactogen-class stimulants in male rats.

Sophia A. Vandewater, Kevin M Creehan, Michael A. Taffe

Neuropharmacology December 2015 DOI: 10.1016/j.neuropharm.2015.08.030 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Experimental animal study Peer reviewed
Population Male Wistar rats
Interventions Mephedrone Methylone MDMA
Dose 0.5 mg/kg/infusion for acquisition; dose-substitution tested 0.0, 0.125, 0.25, 0.5, 1.0, 2.5 mg/kg/inf under FR and 0.125, 1.0 mg/kg/inf under PR
Duration 14 acquisition sessions; long-access sessions of 6 hours
Topics MDMA
Keywords Bath salts Drug addiction Reward Substance abuse
Key findings Mephedrone supported higher intravenous self-administration intake than methylone or MDMA during acquisition and dose-substitution, leading the authors to conclude it is a more effective reinforcer and a higher risk for compulsive use. Long-access 6-hour sessions escalated MDMA intake, though not in the first 2 hours.

Abstract

The intravenous self-administration (IVSA) of 3,4-methylenedioxymethamphetamine (MDMA) is inconsistent in rats, with up to half of subjects failing to acquire reliable drug intake. It is unknown if this changes under long-access conditions (6 h sessions) under which the IVSA of cocaine and methamphetamine escalates. The entactogen class cathinone stimulants which exhibit MDMA-like monoamine effects in the nucleus accumbens, mephedrone (4-methylmethcathinone) and methylone (3,4-methylenedioxymethcathinone), may support more reliable IVSA but results have been mixed. This study was designed to directly compare the IVSA of these three compounds. Groups of male Wistar rats were trained to self-administer mephedrone, methylone or MDMA (0.5 mg/kg/inf) under a Fixed-Ratio (FR) 1 schedule of reinforcement for 14 sessions. Following the acquisition interval, animals were evaluated in FR (0.0, 0.125, 0.25, 0.5, 1.0, 2.5 mg/kg/inf) and Progressive Ratio (PR; 0.125, 1.0 mg/kg/inf) dose-substitution procedures. Long access conditions escalated MDMA intake over the 6 h session but not in the first 2 h. In short access, drug intake was significantly higher in mephedrone-trained rats compared with either the methylone-trained or MDMA-trained groups during acquisition. Mephedrone resulted in the highest intakes during FR and PR dose-substitution in MDMA- and mephedrone-trained groups. Overall it was found that mephedrone is a more effective reinforcer than methylone or MDMA and represents a higher risk for compulsive use.

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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