Previous exposure to (±) 3,4-methylenedioxymethamphetamine produces long-lasting alteration in limbic brain excitability measured by electroencephalogram spectrum analysis, brain metabolism and seizure susceptibility

Giorgi, Filippo Sean; Pizzanelli, Chiara; Ferrucci, Michela; Lazzeri, Gloria; Faetti, M.; Giusiani, Mario; Pontarelli, Fabrizio; Busceti, Carla L.; Murri, Luigi; Fornai, Francesco

doi:10.1016/j.neuroscience.2005.07.036

Cited by 29 publications

(35 citation statements)

References 44 publications

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“…The fMRI results provide evidence that this compromised performance may be related to neural alterations in a range of cortical and sub-cortical structures. This result may reflect the widespread toxic effects of ecstasy on brain 5-HT neurons (Ricaurte et al, 1992a;Fischer et al, 1995;Hatzidimitriou et al, 1999Giorgi et al, 2005Tamburini et al, 2006;Frenzilli et al, 2007;Buscetti et al, 2008) and complements previous reports of functional brain abnormalities during performance of memory tasks in ecstasy users (Daumann et al, 2003a;Daumann et al, 2003b;Daumann et al, 2004a;Jacobsen et al, 2004;Moeller et al, 2004;Daumann et al, 2005). Furthermore, the inclusion of a cannabis group enabled us to separate ecstasy-specific effects (or effects that arise from using both ecstasy and cannabis) from cannabis-specific effects.…”

Section: Discussionsupporting

confidence: 57%

“…The prefrontal cortex has been implicated in retrieval effort or success (Buckner et al, 1998;Zeineth et al, 2003), and although we did not find any associations between memory performance and the PFC, frontal dysregulation in ecstasy users may underlie their worse performance. Giorgi et al (2005) demonstrated the occurrence of metabolic hippocampal hyperexcitability measured by 2-deoxyglucose uptake using experimental models of MDMA administration. Although hippocampal hyperactivation was not evident, the pattern of ecstasy-related hyperactivity is in accord with our findings.…”

Section: Accepted M Manuscriptmentioning

confidence: 97%

“…The most pronounced deficits in ecstasy users appear in learning and memory abilities (Bolla et al 1998;Parrott and Lasky 1998;Morgan et al, 2000;Rodgers et al, 2000;Bhattachary and Powell 2001;Zakzanis and Young 2001;Gouzoulis-Mayfrank et al, 2003;McCardle et al 2004) and evidence suggests that a neurotoxic effect of ecstasy on widespread systems may be responsible for these cognitive impairments (Hatzidimitriou et al, 1999;McCann et al, 2000;Reneman et al, 2001;Giorgi et al, 2005;Tamburini et al, 2006;Frenzilli et al, 2007;Buscetti et al, 2008). Studies using functional magnetic resonance imaging (fMRI) confirmed speculations proposed by Gouzoulis-Mayfrank et al (2003) that the memory dysfunction of ecstasy users might be related to hippocampal dysfunction given that the hippocampus plays a fundamental role in forming new associations or episodic memories (Sperling et al, 2001;Crane and Milner, 2002;Zeineh et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Learning and memory deficits in ecstasy users and their neural correlates during a face-learning task

2009

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It has been consistently shown that ecstasy users display impairments in learning and memory performance. In addition, working memory processing in ecstasy users has been shown to be associated with neural alterations in hippocampal and/or cortical regions as measured by functional magnetic resonance imaging (fMRI). Using functional imaging and a face-learning task, we investigated neural correlates of encoding and recalling face-name associations in 20 recreational drug users whose predominant drug use was ecstasy and 20 controls. To address the potential confounding effects of the cannabis use of the ecstasy using group, a second analysis included 14 previously tested cannabis users (Nestor et al., 2008). Ecstasy users performed significantly worse in learning and memory compared to controls and cannabis users. A conjunction analysis of the encode and recall phases of the task revealed ecstasy-specific hyperactivity in bilateral frontal regions, left temporal, right parietal, bilateral temporal, and bilateral occipital brain regions. Ecstasy-specific hypoactivity was evident in the right dorsal anterior cingulated cortex (ACC) and left posterior cingulated cortex. In both ecstasy and cannabis groups brain activation was decreased in the right medial frontal gyrus, left parahippocampal gyrus, left dorsal cingulate gyrus, and left caudate. These results elucidated ecstasy-related deficits, only some of which might be attributed to cannabis use. These ecstasy-specific effects may be related to the vulnerability of isocortical and allocortical regions to the neurotoxic effects of ecstasy.

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Section: Discussionsupporting

confidence: 57%

Section: Accepted M Manuscriptmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Learning and memory deficits in ecstasy users and their neural correlates during a face-learning task

2009

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“…We have recently observed a situation in which emergency medical intervention was required to recover a monkey after an acute intramuscular dose of 2.4 mg/kg S( + )MDMA, which resulted in seizure and hyperthermia. This was unexpected because the animal had received acute doses of 2.4 mg/kg racemic and R(À)MDMA as well as of 1.7 mg/kg racemic and both enantiomers of MDMA previously and no drug challenges had been administered for 3 months before this event (however, see Giorgi et al, 2005). The LD 50 in rhesus monkeys has been estimated as 22 mg/kg (7)MDMA, i.v.…”

Section: Discussionmentioning

confidence: 99%

Impact of Ambient Temperature on Hyperthermia Induced by (±)3,4-Methylenedioxymethamphetamine in Rhesus Macaques

Huben

Lay

Crean

et al. 2006

Neuropsychopharmacol

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The ambient temperature (T A ) under which rodents are exposed to (7)3,4-methylenedioxymethamphetamine (MDMA) affects the direction and magnitude of the body temperature response, and the degree of hypo/hyperthermia generated in subjects can modify the severity of lasting brain changes in 'neurotoxicity' models. The thermoregulatory effects of MDMA have not been well described in nonhuman primates and it is unknown if T A has the potential to affect acute hyperthermia and therefore other lasting consequences of MDMA. The objective of this study was to determine if the temperature alteration produced by MDMA in nonhuman primates depends on T A as it does in rats and mice. Body temperature and spontaneous home cage activity were monitored continuously in six male rhesus monkeys via radiotelemetry. The subjects were challenged intramuscularly with 0.56-2.4 mg/kg (7)MDMA under each of three T A conditions (18, 24, and 301C) in a randomized order. The temperature was significantly elevated following injection with all doses of MDMA under each ambient temperature. The magnitude of mean temperature change was B11C in most conditions suggesting a closely controlled thermoregulatory response in monkeys across a range of doses and ambient temperatures. Activity levels were generally suppressed by MDMA; however, a 50% increase over vehicle was observed after 0.56 MDMA under the 301C condition. It is concluded that MDMA produces a similar degree of hyperthermia in rhesus monkeys across a range of T A conditions that result in hypothermia or exaggerated hyperthermia in rodents. Monkey temperature responses to MDMA appear to be more similar to humans than to rodents and therefore the monkey may offer an improved model of effects related to MDMA-induced hyperthermia.

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“…Giorgi et al (2005) used a mouse model of MDMA administration and found that MDMA increased hippocampus and entorhinal cortex excitability as measured using electroencephalography, a kainate-induced seizure threshold determination paradigm, and glucose uptake. More globally, 5-HT plays a role in setting the gain for inputs to pyramidal neurons (Higgs et al, 2006) and blocks or reduces seizure activity in multiple seizure models (reviewed by Bagdy et al, 2007), further supporting an overall role for this neurotransmitter of reducing cortical excitability.…”

Section: The Observed Findings May Reflect Altered Cortical Excitabilitymentioning

confidence: 99%

Human Ecstasy Use is Associated with Increased Cortical Excitability: An fMRI Study

Bauernfeind

Dietrich

Blackford

et al. 2011

Neuropsychopharmacol

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The serotonergic neurotoxin, 3,4-methylenedioxymethamphetamine (MDMA/Ecstasy), is a highly popular recreational drug. Human recreational MDMA users have neurocognitive and neuropsychiatric impairments, and human neuroimaging data are consistent with animal reports of serotonin neurotoxicity. However, functional neuroimaging studies have not found consistent effects of MDMA on brain neurophysiology in human users. Several lines of evidence suggest that studying MDMA effects in visual system might reveal the general cortical and subcortical neurophysiological consequences of MDMA use. We used 3 T functional magnetic resonance imaging during visual stimulation to compare visual system lateral geniculate nucleus ( There were no between-group differences in brain activation in any region, but the heaviest MDMA users showed a significantly greater spatial extent of activation than controls in BA 17 (p ¼ 0.031) and BA 18 (p ¼ 0.049). These results suggest that human recreational MDMA use may be associated with a long-lasting increase in cortical excitability, possibly through loss of serotonin input to cortical and subcortical regions. When considered in the context of previous results, cortical hyper-excitability may be a biomarker for MDMA-induced serotonin neurotoxicity.

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Previous exposure to (±) 3,4-methylenedioxymethamphetamine produces long-lasting alteration in limbic brain excitability measured by electroencephalogram spectrum analysis, brain metabolism and seizure susceptibility

Cited by 29 publications

References 44 publications

Learning and memory deficits in ecstasy users and their neural correlates during a face-learning task

Learning and memory deficits in ecstasy users and their neural correlates during a face-learning task

Impact of Ambient Temperature on Hyperthermia Induced by (±)3,4-Methylenedioxymethamphetamine in Rhesus Macaques

Human Ecstasy Use is Associated with Increased Cortical Excitability: An fMRI Study

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