Hippocampal serotonergic damage induced by MDMA (ecstasy): effects on spatial learning

Sprague, Jon E.; Preston, Amanda S.; Leifheit, Michael; Woodside, Brian L.

doi:10.1016/s0031-9384(03)00092-1

Cited by 89 publications

(85 citation statements)

References 40 publications

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“…These results together strengthen the notion that 5HT suppletion after serotonergic drugs such as MDMA and fenfluramine produces spatial memory impairment. In addition, support for this serotonin hypothesis also comes from animal studies that have shown impairment of spatial memory after treatment with MDMA (Sprague et al 2003; Broening et al 2001) or d-fenfluramine (Morford et al 2002 as well. Sprague et al (2003) subsequently linked the MDMA-induced serotonergic lesions in the hippocampus to deficits seen in spatial memory.…”

Section: Discussionmentioning

confidence: 98%

“…In addition, support for this serotonin hypothesis also comes from animal studies that have shown impairment of spatial memory after treatment with MDMA (Sprague et al 2003; Broening et al 2001) or d-fenfluramine (Morford et al 2002 as well. Sprague et al (2003) subsequently linked the MDMA-induced serotonergic lesions in the hippocampus to deficits seen in spatial memory. The overall conclusion that can be drawn from these animal studies is that 5HT plays a direct or indirect role in the observed deficits in spatial memory after treatment with a 5HT agonist or MDMA.…”

Section: Discussionmentioning

confidence: 98%

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Acute dose of MDMA (75 mg) impairs spatial memory for location but leaves contextual processing of visuospatial information unaffected

Kuypers

Ramaekers

2006

Psychopharmacology

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Rationale: Research concerning spatial memory in 3,4-methylenedioxymethamphetamine (MDMA) users has presented conflicting results showing either the presence or absence of spatial memory deficits. Two factors may have confounded results in abstinent users: memory task characteristics and polydrug use. Objectives: The present study aims to assess whether a single dose of MDMA affects spatial memory performance during intoxication and withdrawal phase and whether spatial memory performance after MDMA is task dependent. Materials and methods: Eighteen recreational MDMA users participated in a doubleblind, placebo-controlled, three-way crossover design. They were treated with placebo, MDMA 75 mg, and methylphenidate 20 mg. Memory tests were conducted between 1.5 and 2 h (intoxication phase) and between 25.5 and 26 h (withdrawal phase) post-dosing. Two spatial memory tasks of varying complexity were used that required either storage of stimulus location alone (spatial memory task) or memory for location as well as processing of content or contextual information (change blindness task). Results: After a single dose of MDMA, the subjects made larger localization errors and responded faster compared to placebo in the simple spatial memory task during intoxication phase. Inaccuracy was not due to increased response speed, as determined by regression analysis. Performance in the change blindness task was not affected by MDMA. Methylphenidate did not affect performance on any of the tasks. Conclusion: It is concluded that a single dose of MDMA impairs spatial memory for location but leaves processing of contextual information intact.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

Acute dose of MDMA (75 mg) impairs spatial memory for location but leaves contextual processing of visuospatial information unaffected

Kuypers

Ramaekers

2006

Psychopharmacology

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“…Investigators have frequently proposed that the long-term functional effects of high doses of MDMA are due to the resulting serotonergic deficits measured typically as decreased brain 5-HT and 5-HIAA levels (eg Gurtman et al, 2002;Sprague et al, 2003). In many cases, this hypothesis has been based more on supposition than on supporting data.…”

Section: Discussionmentioning

confidence: 99%

Dissociation of the Neurochemical and Behavioral Toxicology of MDMA (‘Ecstasy’) by Citalopram

Piper

Fraiman

Owens

et al. 2007

Neuropsychopharmacol

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High or repeated doses of the recreational drug 3,4-methylenedioxymethamphetamine (MDMA, or 'Ecstasy') produce long-lasting deficits in several markers of serotonin (5-HT) system integrity and also alter behavioral function. However, it is not yet clear whether MDMA-induced serotonergic neurotoxicity is responsible for these behavioral changes or whether other mechanisms are involved. The present experiment tested the hypothesis that blocking serotonergic neurotoxicity by pretreatment with the selective 5-HT reuptake inhibitor citalopram will also prevent the behavioral and physiological consequences of an MDMA binge administration. Male, SpragueDawley rats (N ¼ 67) received MDMA (4 Â 10 mg/kg) with or without citalopram (10 mg/kg) pretreatment. Core temperature, ejaculatory response, and body weight were monitored during and immediately following drug treatments. A battery of tests assessing motor, cognitive, exploratory, anxiety, and social behaviors was completed during a 10-week period following MDMA administration. Brain tissue was collected at 1 and 10 weeks after drug treatments for measurement of regional 5-HT transporter binding and (for the 1-week samples) 5-HT and 5-HIAA concentrations. Citalopram pretreatment blocked MDMA-related reductions in aggressive and exploratory behavior measured in the social interaction and hole-board tests respectively. Such pretreatment also had the expected protective effect against MDMA-induced 5-HT neurotoxicity at 1 week following the binge. In contrast, citalopram did not prevent most of the acute effects of MDMA (eg hyperthermia and weight loss), nor did it block the decreased motor activity seen in the binge-treated animals 1 day after dosing. These results suggest that some of the behavioral and physiological consequences of a high-dose MDMA regimen in rats are mediated by mechanisms other than the drug's effects on the serotonergic system. Elucidation of these mechanisms requires further study of the influence of MDMA on other neurotransmitter systems.

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“…For example, adult animals treated with the potent serotonin (5-HT)-depleting agent fenfluramine fail to show deficits in the MWM; however, they show deficits in CWM learning Skelton et al 2004) and developmental exposure to fenfluramine induces both CWM and MWM deficits . Administration of MDMA to adult animals produces CWM deficits while producing only memory deficits in the MWM (Sprague et al 2003;Cohen et al 2005;Able et al 2006). …”

Section: Discussionmentioning

confidence: 99%

Treatment with MDMA from P11–20 disrupts spatial learning and path integration learning in adolescent rats but only spatial learning in older rats

Skelton

Williams

2006

Psychopharmacology

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Rationale-Previous studies in rats showed that postnatal day (P)11-20 exposure to ±3,4-methylenedioxymetham-phetamine (MDMA, ecstasy) causes learning and memory deficits in adulthood. The emergence and permanence of these learning deficits are currently unknown.Objective-This study was designed to investigate learning and memory deficits in adolescent (P30 or P40) and older (P180 or P360) rats exposed to MDMA from P11-20.Materials and methods-Within each litter half the animals were exposed to MDMA (20 mg/ kg) and half to saline (SAL) twice a day (8 h apart) from P11-20. In experiment (exp) 1, behavioral testing began on either P30 or P40, whereas in exp 2, testing began on either P180 or P360. Offspring were tested in the Cincinnati water maze (CWM), a test of path integration learning (2 trials/day for 5 days), and the Morris water maze (MWM) (three phases, with 5 days of 4 trials/day and a probe trial on the sixth day per phase).Results-MDMA-treated rats took longer to find the platform and traveled a greater distance to find the platform at all ages tested in all phases of the MWM. MDMA-treated animals also spent less time in the target quadrant during probe trials. In the CWM, P30 and P40 animals took longer to find the goal and committed more errors in locating the goal, while P180 and P360 MDMA-treated animals performed similarly to SAL-treated animals. Conclusion-The data suggest that the spatial learning and memory deficits induced by MDMA are long lasting, while the path integration deficits recover over time.

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Hippocampal serotonergic damage induced by MDMA (ecstasy): effects on spatial learning

Cited by 89 publications

References 40 publications

Acute dose of MDMA (75 mg) impairs spatial memory for location but leaves contextual processing of visuospatial information unaffected

Acute dose of MDMA (75 mg) impairs spatial memory for location but leaves contextual processing of visuospatial information unaffected

Dissociation of the Neurochemical and Behavioral Toxicology of MDMA (‘Ecstasy’) by Citalopram

Treatment with MDMA from P11–20 disrupts spatial learning and path integration learning in adolescent rats but only spatial learning in older rats

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