Toxicity of methylenedioxymethamphetamine (MDMA) in the dog and the rat

Frith, Charles H.; Chang, Louis W.; Lattin, D. L.; Walls, Robert C.; Hamm, Jack; Doblin, Rick

doi:10.1016/0272-0590(87)90158-8

Cited by 53 publications

(22 citation statements)

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“…3.2.1 Motor Activity-MDMA, like other amphetamines, increases locomotion in adults [50,55]. Amphetamine induced hyperactivity in mice emerges at weanling [80].…”

Section: Behavioralmentioning

confidence: 99%

“…Although weight data is commonly obtained in animal studies, the simplicity of measurement belies the numerous factors that can change this index. MDMA alters several physiological processes including reducing food [71] and, to a lesser extent, water intake [39,50]. MDMA also increases urination and defection [8].…”

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confidence: 99%

“…Similarly, adolescent rats lost over ten grams, 8% of pre-drug weight, only hours after MDMA treatments [121]. The molecular mechanisms of MDMA induced weight loss are incompletely understood but are quite likely to involve systemic norepinephrine release by this sympathomimetic and binding to alpha1 or beta3 adrenergic receptors followed by activation Body weight exhibits dose dependent reductions at all exposure ages tested [1,11,50,71,75,76,99,118,119,121,166,167]. Intermittent MDMA (20 mg/kg/day) delivery every fifth day from PD 35 to 60 to rats reduced the rate of weight gain [118,119].…”

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confidence: 99%

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A developmental comparison of the neurobehavioral effects of ecstasy (MDMA)

Piper

2007

Neurotoxicology and Teratology

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The entactogen ±3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a popular recreational drug among college, high school, and, occasionally, middle school students. Preclinical research examining the acute and long-term effects of MDMA has predominately been conducted in reproductively mature subjects but there has been increasing interest in adolescent and in utero exposure. This review examines the acute and long-term responses to MDMA during perinatal, adolescent, and adult periods. The ability of MDMA to alter core body temperature emerges gradually during ontogeny while a reduction in body weight is evident at all ages. Learning and workingmemory are also altered independent of the developmental stage of exposure. Current evidence suggests adults are more sensitive to the long-term serotonin depletions following MDMA but younger ages also exhibit substantial and rapid neuroplasticity. Sexually dimorphic MDMA responses have been identified for the acute hyperthermic and motoric effects of MDMA with pubescent males being especially susceptible. Several physiological, behavioral, and neurochemical MDMA issues requiring further study are also outlined. Keywords±3; 4-methylenedioxymethamphetamine; Adolescence; Anxiety; Depression; Learning; SerotoninThe phenylethylamine ±3,4-methylenedioxymethamphetamine (MDMA) is a popular recreational drug best known as ecstasy. MDMA has several other street names including Adam, baby slits, chocolate chips, clarity, doctor, essence, kleenex, and roll [77]. Although ecstasy has some similarities with both stimulants and hallucinogens, MDMA is an entactogen. Entactogen means "touching within" based on the drug's subjective effects [110]. MDMA also causes long term changes in several markers of the integrity of the serotonin (5-HT) neurotransmitter system [58]. There have been several excellent recent reviews on MDMA toxicology, pharmacokinetics, pharmacodynamics, and neurobehavioral consequences [30,37,113,157], but none have systematically addressed the intricate effects of MDMA during development.Ecstasy use is not restricted to limited subpopulations, that is fans of techno music and "raves" [173] or male homosexuals [73,81], as MDMA has expanded into the general population [124,148,170] and especially young people [52,78,170,172]. Over one hundred pregnant women in Toronto called a substance abuse helpline between 1998 and 2000 to inquire Corresponding Author: Brian J. Piper, Neuroscience and Behavior Program, University of Massachusetts, Amherst, MA 01003-7710, Tel: (413) 545-0996, bpiper@nsm.umass.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers...

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“…3.2.1 Motor Activity-MDMA, like other amphetamines, increases locomotion in adults [50,55]. Amphetamine induced hyperactivity in mice emerges at weanling [80].…”

Section: Behavioralmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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A developmental comparison of the neurobehavioral effects of ecstasy (MDMA)

Piper

2007

Neurotoxicology and Teratology

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“…Drug-related weight changes were anticipated due to the inhibitory effects of both MDMA and citalopram on food intake (Frith et al, 1987;Grignaschi et al, 1998) as well as MDMA stimulation of urination (Bilsky et al, 1991). Therefore, all groups were matched for body weight before dosing, and weight was monitored 2 h after drug treatments and every other day thereafter for 6 days.…”

Section: Physiological Measuresmentioning

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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“…Few studies indicate that MDMA exerts an effect on food consumption in humans (anorectic or bulimic effects) (Shulgin, 1986;Rochester and Kirchner, 1999;Schifano, 2000), as would be expected from its 'substrate-type 5-HT releaser' activity. Furthermore, only one study reports its hypophagic effect in rats (Frith et al, 1987). Curiously, no attempt has been made to investigate the effect of MDMA on feeding behavior in mice and the possible implication of 5-HT receptors.…”

Section: Discussionmentioning

confidence: 99%

3,4-N-Methlenedioxymethamphetamine-Induced Hypophagia is Maintained in 5-HT1B Receptor Knockout Mice, but Suppressed by the 5-HT2C Receptor Antagonist RS102221

Conductier

Crosson

Hen

et al. 2005

Neuropsychopharmacol

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3,4-Methylenedioxy-N-methamphetamine (MDMA or 'ecstasy') is a psychoactive substance, first described as an appetite suppressant in humans, inducing side effects and even death. MDMA increases serotonin (5-HT) levels, and 5-HT inhibits food intake, but the 5-HT receptors involved in MDMA-induced changes in feeding behavior are unknown. We examined whether a systemic MDMA injection would reduce the physiological drive to eat in starved mice and tested if the inactivation of 5-HT 1B or 5-HT 2C receptors could restore this response. Our results indicate that in starved mice, MDMA (10 mg/kg) provoked an initial hypophagia for 1 h (À77%) followed by a period of hyperphagia (studied between 1 and 3 h). This biphasic feeding behavior due to MDMA treatment was maintained in 5-HT 1B receptornull mice or in animals treated with the 5-HT 1B/1D receptor antagonist GR127935 (3 or 10 mg/kg). In contrast, MDMA-induced hypophagia (for the first 1 h period) was suppressed when combined with the 5-HT 2C receptor antagonist RS102221 (2 mg/kg). However, RS102221 did not alter MDMA-induced hyperphagia (for the 1-3 h period) but did exert a stimulant effect, when administered alone, during that period. We have previously shown that MDMA or 5-HT 1A/1B receptor agonist RU24969 fails to stimulate locomotor activity in 5-HT 1B receptor-null mice. Our present data indicate that the 5-HT 2C receptor antagonist RS102221 suppresses MDMA-induced hyperlocomotion. These findings provide the first evidence that the inactivation of 5-HT 2C receptors may reduce hypophagia and motor response to MDMA, while a genetic deficit or pharmacological inactivation of 5-HT 1B receptors was insufficient to alter the feeding response to MDMA.

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Toxicity of methylenedioxymethamphetamine (MDMA) in the dog and the rat

Cited by 53 publications

References 3 publications

A developmental comparison of the neurobehavioral effects of ecstasy (MDMA)

A developmental comparison of the neurobehavioral effects of ecstasy (MDMA)

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

3,4-N-Methlenedioxymethamphetamine-Induced Hypophagia is Maintained in 5-HT1B Receptor Knockout Mice, but Suppressed by the 5-HT2C Receptor Antagonist RS102221

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