Multiple molecular and neuropharmacological effects of MDMA (Ecstasy)

Simantov, Rabi

doi:10.1016/j.lfs.2003.08.002

Cited by 34 publications

(16 citation statements)

References 90 publications

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“…Cole and Sumnall 2003;Green et al 2003;Simantov 2004). Recently, however, Sprague et al (2003) have shown that α 1 adrenoceptors are involved in the hyperthermic response to MDMA, and Fantegrossi et al (2004) reported that the α 1 -adrenoceptor antagonist prazosin blocked the hyperthermia and locomotor increase induced by MDMA in mice.…”

Section: Introductionmentioning

confidence: 99%

α1-Adrenergic receptors mediate the locomotor response to systemic administration of (±)-3,4-methylenedioxymethamphetamine (MDMA) in rats

Selken

Nichols

2007

Pharmacology Biochemistry and Behavior

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The recreational drug 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) increases locomotor activity when administered to rats. Although the published pharmacology of MDMA has focused almost exclusively on the roles of serotonin and dopamine, in vitro studies indicate that MDMA induces serotonin and norepinephrine release with equal potency. The present experiments tested the hypothesis that blockade of α 1 -adrenoceptors with systemic or local administration of the antagonist prazosin would attenuate the locomotor response to systemic administration of (±)-MDMA. Pretreatment with systemic prazosin (0.5 mg/kg) or microinjections into either the prefrontal cortex or ventral tegmental area completely blocked the locomotor stimulant effects of 5 mg/kg (±)-MDMA, assessed using a computerized Behavioral Pattern Monitor. Prazosin was more potent in blocking the locomotor stimulant effects of (±)-MDMA than a 2 mg/kg dose of (+)-amphetamine that produced a similar locomotor activity increase. These results indicate that activation of α 1 -adrenoceptors in both the prefrontal cortex and ventral tegmental areas modulate the locomotor response to MDMA.

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Section: Introductionmentioning

confidence: 99%

α1-Adrenergic receptors mediate the locomotor response to systemic administration of (±)-3,4-methylenedioxymethamphetamine (MDMA) in rats

Selken

Nichols

2007

Pharmacology Biochemistry and Behavior

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“…First, although this review and existing human neuroimaging studies have focused on serotonergic effects of MDMA exposure, it should be made clear that MDMA is a complex pharmacological agent having a broad range of effects across multiple neurotransmitter systems (e.g., Bankson and Cunningham 2001;Green et al 2003;Simantov 2004;Verrico et al 2005;Nair and Gudelsky 2006). Second, the nearly ubiquitous presence of concomitant polydrug use in contemporary MDMA users suggests that much human MDMA research might frequently be better characterized as MDMA-polydrug investigations (e.g., Schifano et al 1998;Pedersen and Skrondal 1999;Gross et al 2002;de Almeida and Silva 2003;Scholey et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Neuroimaging research in human MDMA users: a review

Cowan

2006

Psychopharmacology

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Rationale Determining whether, under what circumstances, and to what extent 3,4-methylenedioxymethamphetamine (MDMA) exposure produces chronic changes in human brain function is a critical public health issue. MDMA is a widely used recreational drug commonly sold as "Ecstasy". Because findings from the animal literature have indicated that specific dosage regimens of MDMA can produce longlasting alterations in serotonergic function, existing studies of MDMA effects in humans have examined brain serotonin (5-HT) transporters (5-HTT) and receptors or have examined brain structures or functions potentially affected by MDMA. Objectives The objectives of this review are to provide a background for interpreting human MDMA neuroimaging research, to examine existing neuroimaging data regarding the rationale for and limitations to human MDMA research, and to provide suggestions for improving the design and interpretation of future neuroimaging approaches. Results Of the existing neuroimaging studies in human MDMA users, few experimental designs have been replicated across different research groups. Only investigations employing nuclear imaging methods to assay brain 5-HTT levels have been replicated across methods and research laboratories. These studies have found reduced levels of the 5-HTT in recently abstinent MDMA users with some evidence for normalization of 5-HTT levels with prolonged abstinence. However, the sensitivity of these methods is unknown.Conclusions The current state of neuroimaging in human MDMA users does not permit conclusions regarding the long-term effects of MDMA exposure. Future study designs might benefit from improved sample homogeneity, increased length of MDMA abstinence, longitudinal study design, test-retest measures, serotonergic specificity, and multimodal approaches.

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“…In adult rats, MDMA causes persistent reductions in 5-HT content, 5-hydroxyindoleacetic acid (5-HIAA) levels, 5-HT transporters, and tryptophan hydroxylase activity (for reviews, see Green et al, 2003;McCann and Ricaurte, 2004;Simantov, 2004). Nonhuman primates show similar changes in 5-HT markers because 5-HIAA and 5-HT transporters are reduced after repeated MDMA exposure (for a review, see Lyles and Cadet, 2003).…”

Section: Introductionmentioning

confidence: 99%

Neonatal 3,4-methylenedioxymethamphetamine (MDMA) exposure alters neuronal protein kinase A activity, serotonin and dopamine content, and [35S]GTPγS binding in adult rats

et al. 2006

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Recreational use of methylenedioxymethamphetamine (MDMA) has dramatically increased among juveniles and young adults of child-bearing age, and the potential for fetal exposure has increased. For this reason, it is surprising that comparatively few studies have assessed the long-term impact of early MDMA exposure on serotonin (5-HT) and dopamine (DA) neurotransmitter systems. The purpose of this study was to determine whether repeated exposure to MDMA during the preweanling period would cause long-term changes in 5-HT and DA functioning. Rats were treated with saline or 20 mg/kg MDMA (two injections per day) from postnatal day (PD) 11-20. At PD 90, rats were killed, and their dorsal striatum, prefrontal cortex, and hippocampus were removed. 5-HT and DA content, as well as their metabolites, were measured using HPLC. In addition, cAMP-dependent protein kinase A (PKA) activity and agonist-stimulated [ 35 S]GTPγS binding was assayed using tissue homogenates from each brain region. Results indicated that early MDMA exposure caused a decrease in PKA activity and 5-HT content in the prefrontal cortex and hippocampus while increasing the efficacy of 5-HT 1A receptors as measured by agonist-stimulated [ 35 S]GTPγS binding. Additionally, DA content was reduced in the dorsal striatum and prefrontal cortex. These data indicate that early MDMA exposure has long-term effects on the 5-HT and DA neurotransmitter systems that may be mediated, at least partially, by changes in 5-HT 1A receptor sensitivity.

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Multiple molecular and neuropharmacological effects of MDMA (Ecstasy)

Cited by 34 publications

References 90 publications

α1-Adrenergic receptors mediate the locomotor response to systemic administration of (±)-3,4-methylenedioxymethamphetamine (MDMA) in rats

α1-Adrenergic receptors mediate the locomotor response to systemic administration of (±)-3,4-methylenedioxymethamphetamine (MDMA) in rats

Neuroimaging research in human MDMA users: a review

Neonatal 3,4-methylenedioxymethamphetamine (MDMA) exposure alters neuronal protein kinase A activity, serotonin and dopamine content, and [35S]GTPγS binding in adult rats

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