Acute MDMA Administration Research Articles

Ecstasy-induced toxicity in rat liver.

The aim of the present study was to examine the effects of single and repeated administration of 3,4-methylenedioxyme-thamphetamine (MDMA, "ecstasy") on rat liver. Animals were given an acute (20 mg/kg) and repeated (20 mg/kg, b.i.d., for 4 consecutive days) intraperitoneal dose of MDMA, and at various times after administration the hepatic and serum determinations were made. The effect of acute MDMA administration included increased triglyceride and cholesterol levels and an increase in all enzyme activities 6 h post administration. The toxic effect of MDMA was also observed in other hepatic processes. Glycogen content showed a marked decrease, which was accompanied by a decrease in serum glucose levels. No significant changes in lipid peroxidation and hepatic GSH content were observed. In contrast, multiple MDMA administration produced some evidence of oxidative stress, namely, increased MDA content and decreased GSH content, a small decrease in liver glycogen at 3 h recovering 6 h post dose, no effect on blood glucose and increased AST and ALP activities but no effects on ALT activity. Seven days after the last MDMA injection a tendency towards recovery was shown. Our results show that the liver toxicity caused by MDMA administration involves several mechanisms.

An appraisal of the pharmacological and toxicological effects of a single oral administration of 3,4-methylenedioxymethamphetamine (MDMA) in the rat.

This study examined some acute pharmacological and toxicological effects of 3,4 methylenedioxymethamphetamine (MDMA, "Ecstasy") over a range of doses (20, 40, 80, 160 and 320 mg/kg orally) in adult female rats. Deaths were observed from the 40 mg/kg MDMA group onwards. Reductions in body weight change, food and water intake were found in the 80 mg/kg group, whilst food intake alone was reduced in the 20 and 40 mg/kg groups. Significant hyperthermic responses were found over the first 8 hr following MDMA administration which were dose-related. A significant hyperactivity of approximately 9 hr duration was observed in the 20 mg/kg and 40 mg/kg groups, whereas there was evidence of a serotonin syndrome in the higher dosage groups. Thus, acute oral administration of MDMA results in a variety of measurable responses. The cause of death in this study is probably a combination of serotonin syndrome and hyperthermia.

Effects of ecstasy on aldosterone secretion in the rat in vivo and in vitro.

This study investigated the effects of Methylenedioxymethamphetamine (MDMA) on aldosterone and renin secretion via, (1) acute administration of MDMA to conscious Wistar rats, and (2) superfusion of whole rat adrenal capsules with 1 microM and 10 microM MDMA, in the presence of 5-HT. In study 1 basal aldosterone levels increased significantly from 3.490 +/- 1.1 nmol/l to 12.099 +/- 2 nmol/l after administration of MDMA (P < 0.05). Control rats showed no significant increase in aldosterone secretion. Basal plasma renin activity (PRA) was 6.86 +/- 1.65 ng/ml/hr in the MDMA treated animals increasing to 228.56 +/- 34.1 ng/ml/hr after administration (P < 0.05). In study 2 the aldosterone response to 5-HT was potentiated by 1 microM and 10 microM MDMA. No consistent stimulation of aldosterone was observed by MDMA alone. In conclusion, acute administration of MDMA to conscious rats causes activation of the renin-angiotensin-aldosterone system. In addition, MDMA can potentiate the direct action of 5-HT on aldosterone secretion in vitro by a mechanism which could be associated with the 5-HT transporter.

The effect of acute MDMA administration on body temperature, serum corticosterone and neurotransmitter concentrations in male and female rats

AbstractThe aim of this study was to examine the effect of acute administration of (±)3,4‐methylenedioxymethamphetamine (MDMA) (20 mg/kg, i.p.) on colonic temperature, serum corticosterone and brain biogenic amine concentrations in group‐housed male and female rats and to determine if there are any gender differences in susceptibility to MDMA‐induced changes. Prior to treatment, basal colonic temperatures were higher in female than in male rats (p &lt;0·05). Temperatures were significantly increased 30 min following MDMA (20 mg/kg, i.p.) in male rats (p &lt;0·05), and 120 min following MDMA in female rats (p &lt;0·05), and were still elevated 240 min following MDMA administration in both sexes. Basal corticosterone concentrations were also higher in female than in male rats (p &lt;0·05), prior to treatment. Serum corticosterone concentrations were significantly elevated in both male and female rates 15 min after MDMA administration (p &lt;0·001), and remained elevated for up to 4 h following MDMA (p &lt;0·001 and p &lt;0·05 respectively). 5‐Hydroxytryptamine (5‐HT) and 5‐hydroxy‐indole‐3‐acetic acid (5‐HIAA) concentrations were significantly depleted in the frontal cortex, hypothalamus and striatum of both male and female rats. However, pineal 5‐HT was resistant to depletion by MDMA in both male and female rats. The 5‐HIAA concentration was significantly reduced in the pineal gland of female rats, probably due to decreased catabolism of pineal 5‐HT. There was a profound decrease in the ratio 5‐HT/5‐HIAA in the frontal cortex but no changes occurred in these ratios in the striatum. hypothalamus or pineal gland in either male or female rats. Dopamine (DA) concentrations were increased and 3,4‐dihydroxyphenyl‐acetic acid (DOPAC) levels decreased in the striatum in both male and female rats 4 h after MDMA administration. The noradrenaline (NA) content of the hypothalamus was increased in male rats 30, 60 and 120 min post MDMA (p &lt;0·05) but no changes were noted in the hypothalamus of female rats. This study indicates that there are slight gender differences in susceptibility to MDMA induced changes in rats.

Effect of ambient temperature on hyperthermia and hyperkinesis induced by 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”) in rats

A stress-free, biotelemetric monitoring technique was used to investigate the effects of ambient temperature (Ta) on the hyperthermic and hyperkinetic effects of 3,4-methylenedioxymethamphetamine. In the first experiment a single injection of 5.0 or 7.5 mg/kg MDMA produced hyperthermia in rats maintained at a Ta of 24 degrees C but hypothermia in rats maintained at a Ta of 11 degrees C for 24 h prior to the injection. In contrast, hyperkinesis was induced at both Tas. In the second experiment, the effects of acute MDMA administration was compared in rats maintained at a standard Ta of 24 degrees C and in rats which were placed in a cool (11 degrees C) room for a brief (90-min) period commencing 30 min after the injection. The brief exposure to the cool environment produced significant attenuation of MDMA-induced hyperthermia but did not affect the magnitude of hyperkinesis. The implications of the results for the understanding of the thermotoxic effects of MDMA in human drug users are discussed.

Inhibition of dopamine release by methylenedioxymethamphetamine is mediated by serotonin

(±)-3,4-Methylenedioxymethamphetamine (MDMA), at doses of 0.1, 1 and 10 mg/kg, produced a long-lasting decrease in extracellular dopamine concentration in the neostriatum of anesthetized rats, as measured by in vivo voltammetry. Since MDMA has been shown to release serotonin from rat brain slices and synaptosomes, we examined the possibility that increased serotonin release might be the cause of the decrease in dopamine release. Rats were treated with d,l-p-chloroamphetamine seven days prior to acute MDMA administration. Rats pretreated with p-chloroamphetamine, which produced a marked decrease in serotonin content, showed no significant decrease in extracellular dopamine concentration when administered 10 mg/kg MDMA. These data suggest that MDMA produces a significant decrease in dopamine release when administered acutely, and that this decrease is an indirect effect mediated by an increase in serotonin release.