Electrophysiologic Changes in Ventral Midbrain Dopaminergic Neurons Resulting from (+/−) -3,4-Methylenedioxymethamphetamine (MDMA—“Ecstasy”)

Federici, Mauro; Sebastianelli, Luca; Natoli, Silvia; Bernardi, Giorgio; Mercuri, Nicola Biagio

doi:10.1016/j.biopsych.2006.11.019

Cited by 8 publications

(4 citation statements)

References 46 publications

(61 reference statements)

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“…Several studies have reported a crosstalk between serotonin and GABA system. Thus, the serotonin releaser MDMA depressed the inhibitory postsynaptic potential of GABAB receptor by activating of 5-HT1B receptor (Federici et al, 2007), and increased GABA efflux in the ventral tegmental brain area (Bankson and Yamamoto, 2004), which correlates with our behavioral data.…”

Section: Discussionsupporting

confidence: 87%

Looking for prosocial genes: ITRAQ analysis of proteins involved in MDMA-induced sociability in mice

Kuteykin-Teplyakov

Maldonado

2014

European Neuropsychopharmacology

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Social behavior plays a fundamental role in life of many animal species, allowing the interaction between individuals and sharing of experiences, needs, and goals across them. In humans, some neuropsychiatric diseases, including anxiety, posttraumatic stress disorder and autism spectrum disorders, are often characterized by impaired sociability. Here we report that N-Methyl-3,4-methylenedioxyamphetamine (MDMA, "Ecstasy") at low dose (3mg/kg) has differential effects on mouse social behavior. In some animals, MDMA promotes sociability without hyperlocomotion, whereas in other mice it elevates locomotor activity without affecting sociability. Both WAY-100635, a selective antagonist of 5-HT1A receptor, and L-368899, a selective oxytocin receptor antagonist, abolish prosocial effects of MDMA. Differential quantitative analysis of brain proteome by isobaric tag for relative and absolute quantification technology (iTRAQ) revealed 21 specific proteins that were highly correlated with sociability, and allowed to distinguish between entactogenic prosocial and hyperlocomotor effects of MDMA on proteome level. Our data suggest particular relevance of neurotransmission mediated by GABA B receptor, as well as proteins involved in energy maintenance for MDMA-induced sociability. Functional association network for differentially expressed proteins in cerebral cortex, hippocampus and amygdala were identified. These results provide new information for understanding the neurobiological substrate of sociability and may help to discover new therapeutic approaches to modulate social behavior in patients suffering from social fear and low sociability.

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Section: Discussionsupporting

confidence: 87%

Looking for prosocial genes: ITRAQ analysis of proteins involved in MDMA-induced sociability in mice

Kuteykin-Teplyakov

Maldonado

2014

European Neuropsychopharmacology

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“…A low dose of MDMA induce a 5-HT 2B receptor-dependent 5-HT release that most likely promotes subsequent DA release in NAcc, while a “high” dose activates also a 5-HT 2B receptor-/5-HT-independent DA release, probably via a direct effect of MDMA on DAT. In this regard, a recent study showed that, according to the dose, MDMA has a dual effect (5-HT dependent or independent) on DA neurons firing [46]. Although some literature supports these observations (i.e., the released 5-HT drives the release of DA), other data showed that fenfluramine, a selective 5-HT releaser, fails to induce DA release [47].…”

Section: Discussionmentioning

confidence: 99%

Role of Serotonin via 5-HT2B Receptors in the Reinforcing Effects of MDMA in Mice

et al. 2009

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The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) reverses dopamine and serotonin transporters to produce efflux of dopamine and serotonin, respectively, in regions of the brain that have been implicated in reward. However, the role of serotonin/dopamine interactions in the behavioral effects of MDMA remains unclear. We previously showed that MDMA-induced locomotion, serotonin and dopamine release are 5-HT2B receptor-dependent. The aim of the present study was to determine the contribution of serotonin and 5-HT2B receptors to the reinforcing properties of MDMA.We show here that 5-HT2B −/− mice do not exhibit behavioral sensitization or conditioned place preference following MDMA (10 mg/kg) injections. In addition, MDMA-induced reinstatement of conditioned place preference after extinction and locomotor sensitization development are each abolished by a 5-HT2B receptor antagonist (RS127445) in wild type mice. Accordingly, MDMA-induced dopamine D1 receptor-dependent phosphorylation of extracellular regulated kinase in nucleus accumbens is abolished in mice lacking functional 5-HT2B receptors. Nevertheless, high doses (30 mg/kg) of MDMA induce dopamine-dependent but serotonin and 5-HT2B receptor-independent behavioral effects.These results underpin the importance of 5-HT2B receptors in the reinforcing properties of MDMA and illustrate the importance of dose-dependent effects of MDMA on serotonin/dopamine interactions.

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“…This is supported by additional observations that suggest serotonergic and dopaminergic systems inhibit NP‐Y (Guy & Pelletier 1988; Pelletier & Simard 1991; Dube et al . 1992) and that serotonin and dopamine are increased in response to METH and MDMA exposure (Samanin & Garattini 1993; Federici et al . 2007).…”

Section: Discussionmentioning

confidence: 99%

“…2002). Considering this, GH levels may be more directly linked to dopamine levels, as studies have shown dopamine increases following exposure to MDMA and METH (Samanin & Garattini 1993; Federici et al . 2007).…”

Section: Discussionmentioning

confidence: 99%

PRECLINICAL STUDY: Changes in leptin, ghrelin, growth hormone and neuropeptide‐Y after an acute model of MDMA and methamphetamine exposure in rats

Kobeissy¹,

Jeung²,

Warren³

et al. 2007

Addiction Biology

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Club drug abuse is a growing problem in the United States. Beyond addiction and toxicity are endocrine effects which are not well characterized. Specifically, the changes in appetite following exposure to drugs of abuse are an interesting but poorly understood phenomenon. Serum hormones such as leptin, ghrelin, growth hormone (GH), and neuropeptide-Y (NP-Y) are known to affect appetite, but have not been studied extensively with drugs of abuse. In this work, we examine the effects of club drugs 3,4-methylenedioxymethamphetamine (MDMA) (ecstasy) and methamphetamine (METH) (doses of 5, 20 and 40 mg/kg) on serum concentrations of these hormones in adult male Sprague-Dawley rats 6, 12, 24 and 48 hours after drug administration. In a dose-dependent manner, MDMA was shown to cause transient significant decreases in serum leptin and GH followed by a base line recovery after 24 hours. Conversely, serum ghrelin increased and normalized after 24 hours. Interestingly, serum NP-Y showed a steady decrease in both treatment of MDMA and METH at different time points and dosages. In humans, abuse of these drugs reduces eating. As evident from these data, acute administration of METH and MDMA had significant effects on different serum hormone levels involved in appetite regulation. Future studies should be performed to see how chronic, low dose drug administration would affect hormone levels and try to answer questions about the physiological mechanisms involved in the anorexic paradigm observed in drug use.

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Electrophysiologic Changes in Ventral Midbrain Dopaminergic Neurons Resulting from (+/−) -3,4-Methylenedioxymethamphetamine (MDMA—“Ecstasy”)

Abstract: Background: Although dopamine (DA) has been implicated in the psychostimulant properties of 3,4-methylenedioxymethamphetamine (MDMA), there is no detailed information on its modalities of action on single ventral midbrain dopaminergic neurons.

Cited by 8 publications

References 46 publications

Looking for prosocial genes: ITRAQ analysis of proteins involved in MDMA-induced sociability in mice

Looking for prosocial genes: ITRAQ analysis of proteins involved in MDMA-induced sociability in mice

Role of Serotonin via 5-HT2B Receptors in the Reinforcing Effects of MDMA in Mice

PRECLINICAL STUDY: Changes in leptin, ghrelin, growth hormone and neuropeptide‐Y after an acute model of MDMA and methamphetamine exposure in rats

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