Relevance of rodent models of intravenous MDMA self-administration to human MDMA consumption patterns

Garza, Richard De La; Fabrizio, Kevin; Gupta, Amita

doi:10.1007/s00213-005-0255-5

Cited by 63 publications

(73 citation statements)

References 61 publications

(85 reference statements)

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“…Murine, rat and monkey experimental models have also shown the rewarding properties of MDMA [109][110][111][112][113][114][115][116]. These models typically make use of conditioned place preference (CPP) tests (which evaluate the preference of an animal for a chamber in which it previously received MDMA) and operant intravenous self-administration tests.…”

Section: Ii6 Rewardingmentioning

confidence: 99%

Mice in Ecstasy: Advanced Animal Models in the Study of MDMA

Stove¹,

Letter²,

Piette³

et al. 2010

CPB

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The party drug 3,4-methylenedioxymethamphetamine -better known as MDMA or ecstasy-has numerous effects on the human body, characterized by a rush of energy, euphoria and empathy. However, also a multitude of toxic/neurotoxic effects have been ascribed to MDMA, based upon case reports and studies in animals. Given the intrinsic difficulties associated with controlled studies in human beings, most of our insights into the biology of MDMA have been gained through animal studies. The vast majority of these studies utilizes a pharmacological approach to elucidate the mechanisms by which MDMA exerts its effects.Advances in genetics during the last decade have led to the development of several mouse models (transgenic or knockout) that have greatly contributed to our understanding of MDMA biology. This review provides an overview of these genetically modified animal models, in the light of some characteristic effects of MDMA, e.g. hyperlocomotion, neurotoxicity, hyperthermia, behaviour or rewarding. Without a shadow of a doubt, the next decade will bring many more advanced animal models, such as mice with site-specific deletion or rescue of genes and more genetically modified rat models. These models will further improve our knowledge on the pharmacology and toxicity of MDMA and, possibly, may assist in developing therapies coping with potential damage in abusers of MDMA and other drugs, as well as in patients suffering from specific neuronal pathologies.MDMA in advanced animal models 3

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Section: Ii6 Rewardingmentioning

confidence: 99%

Mice in Ecstasy: Advanced Animal Models in the Study of MDMA

Stove¹,

Letter²,

Piette³

et al. 2010

CPB

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show abstract

“…Considering that increased 5-HT potency relative to DA appears to reduce reinforcing strength, MDMA might be predicted to be a relatively weaker reinforcer than MA. Research has demonstrated that MDMA, like MA, can function as a positive reinforcer in monkeys (Beardsley et al 1986;Fantegrossi et al 2002;Lamb and Griffiths 1987) and rats (Ratzenboeck et al 2001;Schenk et al 2003), although concerns have recently been raised about the relevance to the human situation of MDMA selfadministration by rats (De La Garza et al 2006). Although these studies did not provide estimates of relative reinforcing strength, MDMA sometimes maintained less responding than other drugs.…”

Section: Introductionmentioning

confidence: 99%

Estimating the relative reinforcing strength of (±)-3,4-methylenedioxymethamphetamine (MDMA) and its isomers in rhesus monkeys: comparison to (+)-methamphetamine

Wang

Woolverton

2006

Psychopharmacology

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Rationale (±)3,4-Methylenedioxymethamphetamine (MDMA) is an analog of methamphetamine (MA) and a drug of abuse. MA, MDMA, and its isomers release monoamine neurotransmitters with varying selectivities and would, therefore, be predicted to vary in their relative strength as reinforcers. Objectives This study compared self-administration of MA, MDMA, and its isomers using a progressive-ratio schedule in rhesus monkeys. Conclusions MDMA and (+)-MDMA were consistent positive reinforcers, but weaker than MA, whereas (−)-MDMA was, at best, a weak reinforcer in some monkeys. The reinforcing strength of MDMA appears to derive primarily from (+)-MDMA. Because MDMA and its isomers have been shown to have relatively higher serotonin to dopamine releasing potency, these data support the hypothesis that increasing 5-HT releasing potency relative to DA is associated with weaker reinforcing effects.

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“…De La Garza et al [46] were relatively unsuccessful in producing self-administration in rats that had been first trained to perform an operant to obtain sucrose pellets. In contrast, another study reported a high number of responses when responding was reinforced by 50 g free base MDMA/infusion during 26 daily sessions [47] .…”

Section: Acquisition Of Mdma Self-administration In Laboratory Animalsmentioning

confidence: 99%

MDMA Self-Administration in Laboratory Animals: A Summary of the Literature and Proposal for Future Research

Schenk

2009

Neuropsychobiology

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The prevalence of 3,4-methylenedioxymethamphetamine (MDMA) use has increased globally and the pattern of consumption has changed considerably. Previously, a subculture of MDMA users was fairly restricted to the dance club scene. More recently, use has spread outside of this subculture and now many users consume MDMA frequently and in large amounts and some meet criteria for drug abuse and/or dependence. Because of confounds associated with studying drug users and abusers, animal models have been employed to investigate potential consequences of drug-taking. Among these, self-administration by laboratory animals has been shown to have excellent predictive validity. There have, however, been mixed results with respect to the ability of MDMA to support and maintain self-administration by laboratory animals. This paper reviews the literature on MDMA self-administration in laboratory primates and rodents. Most of the studies in laboratory animals suggest that only low levels of MDMA are self-administered on a daily basis but some have indicated high levels of self-administered MDMA in certain subjects. Differences might be dependent upon the number of test sessions, prior training conditions or other paradigmatic variables. In most cases, MDMA was found to be a lower efficacy reinforcer than other drugs of abuse. It is suggested that the MDMA self-administration develops following a decrease in MDMA-produced serotonin release that occurs with repeated exposure over an extended period of testing. It is hypothesized that the deficit in central serotonin increases the relative MDMA-produced dopamine responses and that this increase in the dopamine response underlies the development and maintenance of MDMA self-administration.

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Relevance of rodent models of intravenous MDMA self-administration to human MDMA consumption patterns

Cited by 63 publications

References 61 publications

Mice in Ecstasy: Advanced Animal Models in the Study of MDMA

Mice in Ecstasy: Advanced Animal Models in the Study of MDMA

Estimating the relative reinforcing strength of (±)-3,4-methylenedioxymethamphetamine (MDMA) and its isomers in rhesus monkeys: comparison to (+)-methamphetamine

MDMA Self-Administration in Laboratory Animals: A Summary of the Literature and Proposal for Future Research

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