Binge administration of 3,4-methylenedioxymethamphetamine (“ecstasy”) impairs the survival of neural precursors in adult rat dentate gyrus

Hernández‐Rabaza, Vicente; Domínguez-Escribá, Laura; Barcia, Juan A.; Rosel, Jesús; Romero, Francisco J.; García‐Verdugo, José Manuel; Canales, Juan J.

doi:10.1016/j.neuropharm.2006.06.019

Cited by 42 publications

(27 citation statements)

References 51 publications

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“…This study further suggests that the early acceleration of maturation by agomelatine can induce an increase in the survival of newborn granule cells Adult neurogenesis and antidepressant A Soumier et al at a critical period of development. Interestingly, results from our previous study show that 8 days of agomelatine treatment does not affect cell proliferation (Banasr et al, 2006), reinforcing the view of distinct regulation of proliferation vs maturation or survival (Lee et al, 2006;Plumpe et al, 2006;Olson et al, 2006;Hernandez-Rabaza et al, 2006). Consistent with this view, although the agomelatineinduced stimulation of cell proliferation may preferentially involve 5-HT 2C receptor blockade, the increase in cell maturation and survival may be because of a joint action on melatonergic and 5-HT 2C receptors.…”

Section: Adult Neurogenesis and Antidepressantmentioning

confidence: 52%

Mechanisms Contributing to the Phase-Dependent Regulation of Neurogenesis by the Novel Antidepressant, Agomelatine, in the Adult Rat Hippocampus

Soumier¹,

Banasr²,

Lortet³

et al. 2009

Neuropsychopharmacol

145

138

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Agomelatine is a novel antidepressant acting as a melatonergic receptor agonist and serotonergic (5-HT 2C ) receptor antagonist. In adult rats, chronic agomelatine treatment enhanced cell proliferation and neurogenesis in the ventral hippocampus (VH), a region pertinent to mood disorders. This study compared the effects of agomelatine on cell proliferation, maturation, and survival and investigated the cellular mechanisms underlying these effects. Agomelatine increased the ratio of mature vs immature neurons and enhanced neurite outgrowth of granular cells, suggesting an acceleration of maturation. The influence of agomelatine on maturation and survival was accompanied by a selective increase in the levels of BDNF (brain-derived neurotrophic factor) vs those of VEGF (vascular endothelial factor) and IGF-1 (insulin-like growth factor 1), which were not affected. Agomelatine also activated several cellular signals (extracellular signal-regulated kinase1/2, protein kinase B, and glycogen synthase kinase 3b) known to be modulated by antidepressants and implicated in the control of proliferation/survival. Furthermore, as agomelatine possesses both melatonergic agonist and serotonergic (5-HT 2C ) antagonist properties, we determined whether melatonin and 5-HT 2C receptor antagonists similarly influence cell proliferation and survival. Only the 5-HT 2C receptor antagonists, SB243,213 or S32006, but not melatonin, mimicked the effects of agomelatine on cell proliferation in VH. The promoting effect of agomelatine on survival was not reproduced by the 5-HT 2C receptor antagonists or melatonin alone. However, it was blocked by a melatonin antagonist, S22153. These results show that agomelatine treatment facilitates all stages of neurogenesis and suggest that a joint effect of melatonin agonism and 5HT 2C antagonism may be involved in promotion by agomelatine of survival in the hippocampus.

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Section: Adult Neurogenesis and Antidepressantmentioning

confidence: 52%

Mechanisms Contributing to the Phase-Dependent Regulation of Neurogenesis by the Novel Antidepressant, Agomelatine, in the Adult Rat Hippocampus

Soumier¹,

Banasr²,

Lortet³

et al. 2009

Neuropsychopharmacol

145

138

View full text Add to dashboard Cite

show abstract

“…Such impairments have been linked to various forms of drug-induced cognitive dysfunction, including contextual learning, spatial working memory and cognitive flexibility [14]. Alcohol, when administered in binge-like fashion to adult rats, decreased neural progenitor proliferation and long-term survival of newborn cells [37], whereas MDMA only altered survival rates [38]. …”

Section: Discussionmentioning

confidence: 99%

Prenatal Exposure to Alcohol and 3,4-Methylenedioxymethamphetamine (Ecstasy) Alters Adult Hippocampal Neurogenesis and Causes Enduring Memory Deficits

Canales

Ferrer-Donato²

2014

Dev Neurosci

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Recreational drug use among pregnant women is a source of concern due to potential harmful effects of drug exposure on prenatal and infant development. The simultaneous abuse of ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] and alcohol is prevalent among young adults, including young expectant mothers. Here, we used a rat model to study the potential risks associated with exposure to alcohol and MDMA during pregnancy. Pregnant rats received alcohol, MDMA, or both alcohol and MDMA by gavage at E13 through E15 twice daily. Female offspring treated prenatally with the combination of alcohol and MDMA, but not those exposed to either drug separately, showed at 3 months of age decreased exploratory activity and impaired working memory function. Prenatal treatment with the combination of alcohol and MDMA decreased proliferation of neuronal precursors in the adult dentate gyrus of the hippocampus, as measured by 5-bromo-2-deoxyuridine labelling, and adult neurogenesis, assessed by quantifying doublecortin expression. These results provide the first evidence that the simultaneous abuse of alcohol and ecstasy during pregnancy, even for short periods of time, may cause significant abnormalities in neurocognitive development.

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“…Of note is that the extent of the observed neuronal degeneration generally correlated with the degree of hyperthermia achieved. Importantly, MDMA binge administration to rats (eight injections of 5 mg/kg at 6-h intervals) was shown to significantly decrease the survival rate of cells incorporated in the granular layer of the HIP dentate gyrus of about 50% and of those remaining in the subgranular layer by approximately 30%, thereby affecting the neurogenesis process [285]. Also, in the rat brain, astroglial activation and Hsp27 overexpression, a molecular chaperone, were found in the HIP CA1 region after a single dose of 30 mg/kg MDMA, which may indicate a particular vulnerability of this region [286].…”

Section: Mdma-induced Neurotoxicity To the Rat-biochemical And Histolmentioning

confidence: 97%

Molecular and Cellular Mechanisms of Ecstasy-Induced Neurotoxicity: An Overview

et al. 2009

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"Ecstasy" [(+/-)-3,4-methylenedioxymethamphetamine, MDMA, XTC, X, E] is a psychoactive recreational hallucinogenic substance and a major worldwide drug of abuse. Several reports raised the concern that MDMA has the ability to induce neurotoxic effects both in laboratory animals and humans. Despite more than two decades of research, the mechanisms by which MDMA is neurotoxic are still to be fully elucidated. MDMA induces serotonergic terminal loss in rats and also in some mice strains, but also a broader neuronal degeneration throughout several brain areas such as the cortex, hippocampus, and striatum. Meanwhile, in human "ecstasy" abusers, there are evidences for deficits in seronergic biochemical markers, which correlate with long-term impairments in memory and learning. There are several factors that contribute to MDMA-induced neurotoxicity, namely, hyperthermia, monoamine oxidase metabolism of dopamine and serotonin, dopamine oxidation, the serotonin transporter action, nitric oxide, and the formation of peroxinitrite, glutamate excitotoxicity, serotonin 2A receptor agonism, and, importantly, the formation of MDMA neurotoxic metabolites. The present review covered the following topics: history and epidemiology, pharmacological mechanisms, metabolic pathways and the influence of isoenzyme genetic polymorphisms, as well as the acute effects of MDMA in laboratory animals and humans, with a special focus on MDMA-induced neurotoxic effects at the cellular and molecular level. The main aim of this review was to contribute to the understanding of the cellular and molecular mechanisms involved in MDMA neurotoxicity, which can help in the development of therapeutic approaches to prevent or treat the long-term neuropsychiatric complications of MDMA abuse in humans.

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Binge administration of 3,4-methylenedioxymethamphetamine (“ecstasy”) impairs the survival of neural precursors in adult rat dentate gyrus

Cited by 42 publications

References 51 publications

Mechanisms Contributing to the Phase-Dependent Regulation of Neurogenesis by the Novel Antidepressant, Agomelatine, in the Adult Rat Hippocampus

Mechanisms Contributing to the Phase-Dependent Regulation of Neurogenesis by the Novel Antidepressant, Agomelatine, in the Adult Rat Hippocampus

Prenatal Exposure to Alcohol and 3,4-Methylenedioxymethamphetamine (Ecstasy) Alters Adult Hippocampal Neurogenesis and Causes Enduring Memory Deficits

Molecular and Cellular Mechanisms of Ecstasy-Induced Neurotoxicity: An Overview

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