Effects of dose, sex, and long-term abstention from use on toxic effects of MDMA (ecstasy) on brain serotonin neurons

Reneman, Liesbeth; Booij, Jan; Bruin, Kora de; Reitsma, Johannes B.; Wolff, Frederik A. de; Gunning, W. Boudewijn; Heeten, Gerard J. den; Brink, Wim van den

doi:10.1016/s0140-6736(01)06888-x

Cited by 202 publications

(189 citation statements)

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“…Gender was also found to moderate the extent of ecstasy-related deficits in design fluency (with female users exhibiting a deficit while male users actually performed better than controls) although it was not a moderating factor on deficits observed in verbal learning (Medina et al, 2005). Reneman et al (2001) found that female ecstasy users exhibited a larger reduction in serotonin transporter densities relative to males.…”

Section: Discussionmentioning

confidence: 92%

Prospective memory functioning among ecstasy/polydrug users: evidence from the Cambridge Prospective Memory Test (CAMPROMPT)

et al. 2011

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Rationale: Prospective memory (PM) deficits in recreational drug users have been documented in recent years. However the assessment of PM has largely been restricted to self report measures that fail to capture the distinction between event based and time based PM.The aim of the present study is to address this limitation.Objectives: Extending our previous research we augmented the range laboratory measures of PM by employing the CAMPROMPT test battery to investigate the impact of illicit drug use on prospective remembering in a sample of cannabis only, ecstasy/polydrug and non users of illicit drugs, separating event and time based PM performance. We also administered measures of executive function and retrospective memory in order to establish whether ecstasy/polydrug deficits in PM were mediated by group differences in these processes.Results: Ecstasy/polydrug users performed significantly worse on both event and time based prospective memory tasks in comparison to both cannabis only and non user groups.Furthermore, it was found that across the whole sample, better retrospective memory and executive functioning was associated with superior PM performance. Nevertheless, this association did not mediate the drug-related effects that were observed. Consistent with our previous study, recreational use of cocaine was linked to PM deficits.Conclusions: PM deficits have again been found among ecstasy/polydrug users which appear to be unrelated to group differences in executive function and retrospective memory.However, the possibility that these are attributable to cocaine use cannot be excluded.Prospective memory (PM) involves remembering to execute a particular behaviour at some future point in time which may be in the short or long term, for example remembering to turn off the lights when leaving a room or remembering to attend a meeting, meet a friend or pass on a message. Self report measures of this construct have been developed (e.g., Crawford et al., 2005;Hannon et al., 1995) and in previous research from our laboratory, Fisk and co-workers have demonstrated apparent impairments on these measures among ecstasy/polydrug users (Montgomery & Fisk, 2007) and cannabis only users (Fisk & Montgomery, 2008). Other researchers have also reported deficits on self report PM measures among users of illicit drugs (Heffernan et al., 2001a;2001b;Rodgers et al., 2001; and studies from our own laboratory and elsewhere have revealed deficits among illicit drug users in laboratory measures of PM (Hadjiefthyvoulou et al., in press;Rendell et al., 2007a;Rendell et al., 2009).Unsurprisingly, given their role in supporting memory functions in general, evidence suggests that PM is dependent on medial temporal-hippocampal processes. For example, in a clinical group with medial temporal sclerosis, Adda et al. (2008) found that PM performance was impaired and that among those with left hemisphere lesions the degree of impairment was correlated with that in delayed (7 day) verbal recall on the Rey Auditory Verbal Learning Task ...

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Section: Discussionmentioning

confidence: 92%

Prospective memory functioning among ecstasy/polydrug users: evidence from the Cambridge Prospective Memory Test (CAMPROMPT)

et al. 2011

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“…Since studies in non-human primates showed long-term and possible irreversible damage of serotonergic axons in the cerebral cortex induced by MDMA (Hatzidimitriou et al, 1999), assessment of SERT density in the cerebral cortex is especially important for studying the neurotoxic effects of ecstasy. Reductions of SERT densities in cortical brain regions were reported in male (Semple et al, 1999) and female (Reneman et al, 2001b) ecstasy users. However, others discussed these results because of the presumed limited sensitivity of [ 123 I]b-CIT SPECT imaging to measure SERT density in the cerebral cortex (Heinz and Jones, 2000;Ricaurte and McCann, 2001;Kish, 2002).…”

Section: Introductionmentioning

confidence: 94%

Validation of [123I]β-CIT SPECT to Assess Serotonin Transporters In Vivo in Humans: a Double-Blind, Placebo-Controlled, Crossover Study with the Selective Serotonin Reuptake Inhibitor Citalopram

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et al. 2005

Neuropsychopharmacol

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“…247 There is evidence to indicate that MDMA has neurotoxic effects on the 5-HTergic system in animals 248 and humans, 249,250 mainly characterized by a decreased number of serotonin transporters. 249,251 Animal studies have indicated that MDMA administration results in long-term attenuation of brain 5-HT and 5-HIAA as well as attenuated TPH activity and reductions in the density of 5-HT uptake sites (for review see Curran et al 252 ) and there is evidence to indicate that recovery may remain incomplete for several years. 253,254 In human studies the decreased 5-HTT binding is generally reported to be at least partly reversible.…”

Section: 4-methylenedioxymethamphetamine (Mdma)mentioning

confidence: 99%

“…253,254 In human studies the decreased 5-HTT binding is generally reported to be at least partly reversible. 249,251,255,256 However, it should be mentioned that the recovery of 5-HTT densities does not necessarily guarantee normal functioning. 257 Studies on the functional consequences of MDMA induced 5-HT neurotoxicity show converging evidence of memory impairments.…”

Section: 4-methylenedioxymethamphetamine (Mdma)mentioning

confidence: 99%

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Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

et al. 2006

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In recent years, the term serotonergic vulnerability (SV) has been used in scientific literature, but so far it has not been explicitly defined. This review article attempts to elucidate the SV concept. SV can be defined as increased sensitivity to natural or experimental alterations of the serotonergic (5-HTergic) system. Several factors that may disrupt the 5-HTergic system and hence contribute to SV are discussed, including genetic factors, female gender, personality characteristics, several types of stress and drug use. It is explained that SV can be demonstrated by means of manipulations of the 5-HTergic system, such as 5-HT challenges or acute tryptophan depletion (ATD). Results of 5-HT challenge studies and ATD studies are discussed in terms of their implications for the concept of SV. A model is proposed in which a combination of various factors that may compromise 5-HT functioning in one person can result in depression or other 5-HT-related pathology. By manipulating 5-HT levels, in particular with ATD, vulnerable subjects may be identified before pathology initiates, providing the opportunity to take preventive action. Although it is not likely that this model applies to all cases of depression, or is able to identify all vulnerable subjects, the strength of the model is that it may enable identification of vulnerable subjects before the 5-HT related pathology occurs. Molecular Psychiatry ( Keywords: serotonin; mood disorders; stress; genetics; sex; tryptophan Involvement of serotonin in depressionMood disorders are one of the most prevalent forms of mental illness. 1 According to the DSM-IV, the lifetime risk for major depressive disorder is between 10 and 25% for women and between 5 and 12% for men. 2 Depression has been studied intensively during the last few decades, but the psychological and neurobiological determinants of depression have not yet been precisely defined. Although several factors are known to contribute to the etiology of depression, it is not clear how these factors cause depression, and why some subjects become depressed while others remain unaffected. In terms of biological factors in the etiology of depression, there are several hypotheses. These include neurotransmitter dysfunctions (serotonin, 5-HT; dopamine, DA; norepinephrine, NE); dysregulations in hypothalamic-pituitary-adrenal (HPA) axis activity; and immune system imbalance. The aim of this article is not to discuss all of these hypotheses in detail, but to evaluate the role that serotonin may play within these hypothesized mechanisms.It is widely accepted that diminished serotonergic (5-HTergic) function is involved in the onset and course of depression. 3,4 The 5-HTergic system is a large and complex system. Although nearly all cell bodies of 5-HTergic neurons are located in the raphe nuclei in the brain stem, the axons of these neurons innervate almost the entire brain. The actions of 5-HT are mediated by 16 types and subtypes of receptors. 5 As the 5-HTergic system is assumed to be a modulatory system, the exact func...

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Effects of dose, sex, and long-term abstention from use on toxic effects of MDMA (ecstasy) on brain serotonin neurons

Cited by 202 publications

References 21 publications

Prospective memory functioning among ecstasy/polydrug users: evidence from the Cambridge Prospective Memory Test (CAMPROMPT)

Prospective memory functioning among ecstasy/polydrug users: evidence from the Cambridge Prospective Memory Test (CAMPROMPT)

Validation of [123I]β-CIT SPECT to Assess Serotonin Transporters In Vivo in Humans: a Double-Blind, Placebo-Controlled, Crossover Study with the Selective Serotonin Reuptake Inhibitor Citalopram

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

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