Changes in serotonin, dopamine and noradrenaline levels in striatum and nucleus accumbens after repeated administration of the abused drug MDMA in rats

Mayerhofer, Andreas; Kovar, Karl‐Artur; Schmidt, Werner

doi:10.1016/s0304-3940(01)01992-9

Cited by 56 publications

(39 citation statements)

References 18 publications

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“…There is also clear experimental evidence suggesting that MDMA increases not only the extracellular level of DA but also of 5-HT in the brain (Gough et al 1991;Mayerhofer et al 2001). Accordingly, we observed an increase of the spontaneous firing of the DAergic cells at a low concentration of MDMA and, using higher concentrations, when the D2 receptors were blocked.…”

Section: Discussionsupporting

confidence: 66%

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

Federici

Sebastianelli

Natoli

et al. 2007

Biological Psychiatry

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Section: Discussionsupporting

confidence: 66%

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

Federici

Sebastianelli

Natoli

et al. 2007

Biological Psychiatry

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“…Given the well-known role of DA in modulating activity, it is possible that the reduced ambulation and rearing observed in the MDMA-treated animals was due to abnormalities in the dopaminergic system. In addition to the previously mentioned ability of high MDMA doses to acutely release catecholamines, longer lasting alterations in catecholaminergic function have been reported not only in mice (which are known to exhibit dopamine neurotoxicity following MDMA), but also in rats, monkeys, and humans exposed to this compound (Commins et al, 1987;Gerra et al, 2002Gerra et al, , 2003Mayerhofer et al, 2001;McCann et al, 1994;Ricaurte et al, 1992). Moreover, we recently found that the same MDMA binge regimen used in the present study (ie with a 1-h interdose interval) significantly reduced DA transporter binding in the striatum .…”

Section: Discussionmentioning

confidence: 94%

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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“…All of these effects may be related to the high affinity of MDMA for the NET, capacity of MDMA to release NE, and agonist effects at α2-adrenoceptor receptors (Lavelle et al 1999). Notably, high doses of MDMA can deplete DA and NE in rat and guinea pig brains (Commins et al 1987;Mayerhofer et al 2001). Thus, the high affinity of MDMA as a substrate for the human NET warrants further consideration, particularly in devising medications to treat the consequences of acute or repeated exposure to MDMA.…”

Section: Discussionmentioning

confidence: 99%

“…Serotonin neurons of the primate brain are more susceptible to MDMA-induced changes when compared to rats (Ricaurte and McCann 1992;Slikker et al 1988Slikker et al , 1989, whereas in mice, MDMA selectively modifies DA neurons while sparing 5-HT neurons (Logan et al 1988;O'Callaghan and Miller 1994;Xie et al 2004). Dose and dosing regimen are another contributing factor to MDMA-induced neurotoxicity, as high doses of MDMA promotes dopaminergic and noradrenergic neurotoxicity in rats (Commins et al 1987;Mayerhofer et al 2001). However, the susceptibility of catecholamine neurons to MDMA-induced neurotoxicity is unresolved in primates (Turner and Parrott 2000).…”

Section: Introductionmentioning

confidence: 99%

MDMA (Ecstasy) and human dopamine, norepinephrine, and serotonin transporters: implications for MDMA-induced neurotoxicity and treatment

2005

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Rationale: 3,4-Methylenedioxymethamphetamine (MDMA, designated as "Ecstasy" if illicitly marketed in tablet form) induces significant decrements in neuronal serotonin (5-HT) markers in humans, nonhuman primates, and rats as a function of dosing and dosing regimen. In rats, MDMA-mediated effects are attributed, in part, to selective high-affinity transport of MDMA The affinity of MDMA for the human SERT in transfected cells does not clarify the apparent selective toxicity of MDMA for serotonin neurons, although conceivably, its higher efficacy for stimulating 5-HT release may be a distinguishing factor. The findings highlight the need to investigate MDMA effects in DAT-, SERT-, and NET-expressing neurons in the primate brain and the therapeutic potential of NET or DAT inhibitors, in addition to SERT-selective inhibitors, for alleviating the pharmacological effects of MDMA.

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Changes in serotonin, dopamine and noradrenaline levels in striatum and nucleus accumbens after repeated administration of the abused drug MDMA in rats

Cited by 56 publications

References 18 publications

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

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

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

MDMA (Ecstasy) and human dopamine, norepinephrine, and serotonin transporters: implications for MDMA-induced neurotoxicity and treatment

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