Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat

Malberg, Jessica E.; Seiden, Lewis S.

doi:10.1523/jneurosci.18-13-05086.1998

Cited by 314 publications

(310 citation statements)

References 53 publications

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“…In the present study, MDMA induced an increase in rectal temperature of approximately 2.56°C 1 h after drug injection at the highest dose (40 mg/kg), which is in agreement with previous studies using the same dose [27,41,42]. Fifty minutes after the drug administration, two rats (one receiving 20 mg/kg and another receiving 40 mg/kg) suffered from tremor, muscular rigidity, bruxism and tachycardia.…”

Section: Physiological Changessupporting

confidence: 93%

Effects of MDMA on blood glucose levels and brain glucose metabolism

Soto-Montenegro

Vaquero

Arango

et al. 2007

Eur J Nucl Med Mol Imaging

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Purpose This study was designed to assess changes in glucose metabolism in rats administered single or repeated doses of MDMA. Methods Two different experiments were performed: (1) A single-dose study with four groups receiving 20 mg/kg, 40 mg/kg, saline or heat, and (2) a repeated-dose study with two groups receiving three doses, at intervals of 2 h, of 5 mg/kg or saline. Rats were imaged using a dedicated small-animal PET scanner 1 h after single-dose administration or 7 days after repeated doses. Glucose metabolism was measured in 12 cerebral regions of interest. Rectal temperature and blood glucose were monitored. Results Peak body temperature was reached 1 h after MDMA administration. Blood glucose levels decreased significantly after MDMA administration. In the single-dose experiment, brain glucose metabolism showed hyperactivation in cerebellum and hypo-activation in the hippocampus, amygdala and auditory cortex. In the repeated-dose experiment, brain glucose metabolism did not show any significant change at day 7.Conclusion These results are the first to indicate that MDMA has the potential to produce significant hypoglycaemia. In addition, they show that MDMA alters glucose metabolism in components of the motor, limbic and somatosensory systems acutely but not on a long-term basis.

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Section: Physiological Changessupporting

confidence: 93%

Effects of MDMA on blood glucose levels and brain glucose metabolism

Soto-Montenegro

Vaquero

Arango

et al. 2007

Eur J Nucl Med Mol Imaging

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“…The loss of serotonin in the present study occurred with only modest temperature increases. Elevated temperature exacerbates the serotonin loss after MDMA (Colado et al 1993;Malberg and Seiden 1998), but loss can occur without markedly elevated temperatures (McGregor et al 2003). The present results suggest that "harm reduction" approaches by limiting hyperthermia are not a guarantee against serotonin depletion.…”

Section: Discussionmentioning

confidence: 66%

Sex differences in the neurochemical and functional effects of MDMA in Sprague–Dawley rats

et al. 2006

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Rationale 3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy") use has been associated with acute toxicities and persistent depletion of the neurotransmitter serotonin (5-HT). Objectives This study investigates whether sex differences in the acute and long-term effects of MDMA exist. Methods Male and female rats received saline or 15 mg/kg MDMA, ip, bid for 4 days. Temperature was monitored on days 1 and 4. Locomotor activity was measured in a second cohort of animals on days 1 and 4 and after recovery on day 14. The effects of MDMA on performance in a plus maze task and brain levels of serotonin (5-HT) and the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were determined in a third cohort of animals 2 weeks after the last MDMA treatment. Results Locomotor activity and temperature increased after MDMA administration on day 1. The drug-induced increases in temperature but not locomotion attenuated with repeated MDMA administration. Male and female MDMA-treated rats spent less time in the open arms of the elevated plus maze and had less 5-HT and 5-HIAA in all brain regions 2 weeks after the end of treatment. Temperature effects of MDMA and persistent effects on plus maze and brain serotonin content were similar in males and females. In contrast, females exhibited markedly greater locomotor stimulation after acute MDMA and also showed sensitization to an acute challenge 2 weeks later. Conclusions MDMA elicits substantially greater locomotor activation in female rats than in males, but persistent effects on anxiety and serotonin content were similar in males and females.

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“…Room temperature was maintained at an ambient temperature of 281C by a reverse-cycle air conditioner. High temperatures may exacerbate the neurotoxic effects of MDMA in rats (Malberg and Seiden, 1998) and better simulate the conditions under which MDMA is often taken by humans.…”

Section: Methodsmentioning

confidence: 99%

Chronic Fluoxetine Treatment Partly Attenuates the Long-Term Anxiety and Depressive Symptoms Induced by MDMA (‘Ecstasy’) in Rats

Thompson

Clemens

et al. 2003

Neuropsychopharmacol

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Use of the drug 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') can have long-term adverse effects on emotion in both humans and laboratory animals. The present study examined whether chronic treatment with the antidepressant drug fluoxetine could reverse such effects. Male Wistar rats were briefly exposed to MDMA (4 Â 5 mg/kg over 4 h) or vehicle on 2 consecutive days. Approximately 9-12 weeks later, half of the rats received a dose of approximately 6 mg/kg/day fluoxetine in their drinking water for a 5-week period. Fluoxetine administration reduced fluid intake and body weight in MDMA and vehicle pretreated rats. After several weeks of fluoxetine treatment, rats were assessed on the social interaction test, the emergence test of anxiety and the forced swim model of depression. MDMA pretreated rats showed reduced social interaction, increased anxiety on the emergence test, and increased immobility and decreased active responses in the forced swim test. Fluoxetine treatment reversed MDMA-induced anxiety in the emergence test and depressive-like effects in the forced swim test, yet exhibited no effects on the social interaction test. MDMA pretreated rats had decreased 5-HT and 5-HIAA levels in limbic and cortical regions, and decreased density of serotonin transporter sites in the cortex. Fluoxetine treatment did not greatly affect 5-HT levels in MDMA pretreated rats, but significantly decreased 5-HIAA levels in all brain sites examined. Postmortem blood serum levels of fluoxetine and norfluoxetine did not differ in MDMA and vehicle pretreated rats. These results indicate that fluoxetine may provide a treatment option for some of the deleterious long-term effects resulting from MDMA exposure.

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Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat

Cited by 314 publications

References 53 publications

Effects of MDMA on blood glucose levels and brain glucose metabolism

Effects of MDMA on blood glucose levels and brain glucose metabolism

Sex differences in the neurochemical and functional effects of MDMA in Sprague–Dawley rats

Chronic Fluoxetine Treatment Partly Attenuates the Long-Term Anxiety and Depressive Symptoms Induced by MDMA (‘Ecstasy’) in Rats

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