Disposition of methylenedioxymethamphetamine and three metabolites in the brains of different rat strains and their possible roles in acute serotonin depletion

Chu, Teresa; Kumagai, Yoshito; DiStefano, Emma; Cho, Arthur K.

doi:10.1016/0006-2952(95)02397-6

Cited by 134 publications

(104 citation statements)

References 18 publications

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“…The pattern of responding after administration of 1.0 mg/kg MDPV was quite similar, and it seems likely that a higher dose of MDPV would look very similar indeed to what we have previously seen with 3.0 mg/ kg MDMA. We have also reported that cumulative doses of MDMA lead to higher concentrations of MDMA in plasma, 3,4-Methylenedioxypyrovalerone in mice WE Fantegrossi et al as compared with administration of an equivalent bolus dose, revealing that, consistent with previous studies in rats (Chu et al, 1996), squirrel monkeys (Mechan et al, 2006;Mueller et al, 2008), and humans (de la Torre et al, 2000), metabolism is also decreased when the dose is administered cumulatively in the mouse . Analogous studies have not yet been performed with MDPV, but it is possible that this compound also displays nonlinear pharmacokinetics, which may explain the apparent potency differences here observed when the drug was administered cumulatively, vs when it was given as a single bolus dose.…”

Section: 4-methylenedioxypyrovalerone In Micesupporting

confidence: 86%

In vivo Effects of Abused ‘Bath Salt’ Constituent 3,4-methylenedioxypyrovalerone (MDPV) in Mice: Drug Discrimination, Thermoregulation, and Locomotor Activity

Fantegrossi

Gannon

Zimmerman

et al. 2012

Neuropsychopharmacol

138

151

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In recent years, synthetic analogues of naturally occurring cathinone have emerged as psychostimulant-like drugs of abuse in commercial 'bath salt' preparations. 3,4-Methylenedioxypyrovalerone (MDPV) is a common constituent of these illicit products, and its structural similarities to the more well-known drugs of abuse 3,4-methylenedioxymethamphetamine (MDMA), and methamphetamine (METH) suggest that it may have similar in vivo effects to these substances. In these studies, adult male NIH Swiss mice were trained to discriminate 0.3 mg/kg MDPV from saline, and the interoceptive effects of a range of substitution doses of MDPV, MDMA, and METH were then assessed. In separate groups of mice, surgically implanted radiotelemetry probes simultaneously monitored thermoregulatory and locomotor responses to various doses of MDPV and MDMA, as a function of ambient temperature. We found that mice reliably discriminated the MDPV training dose from saline and that cumulative doses of MDPV, MDMA, and METH fully substituted for the MDPV training stimulus. All three drugs had similar ED 50 values in this procedure. Stimulation of motor activity was observed following administration of a wide range of MDPV doses (1-30 mg/kg), and the warm ambient temperature potentiated motor activity and elicited profound stereotypy and self-injurious behavior at 30 mg/kg. In contrast, MDPV-induced hyperthermic effects were observed in only the warm ambient environment. This pattern of effects is in sharp contrast to MDMA, where ambient temperature interacts with thermoregulation, but not locomotor activity. These studies suggest that although the interoceptive effects of MDPV are similar to those of MDMA and METH, direct effects on thermoregulatory processes and locomotor activity are likely mediated by different mechanisms than those of MDMA.

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Section: 4-methylenedioxypyrovalerone In Micesupporting

confidence: 86%

In vivo Effects of Abused ‘Bath Salt’ Constituent 3,4-methylenedioxypyrovalerone (MDPV) in Mice: Drug Discrimination, Thermoregulation, and Locomotor Activity

Fantegrossi

Gannon

Zimmerman

et al. 2012

Neuropsychopharmacol

138

151

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“…Previous studies in rodents have shown that male and female rats have comparable brain levels of MDMA after acute treatment (Chu et al 1996). In the present study, the acute hyperthermic effects of MDMA as well as the persevering effects on both serotonin and anxiety were comparable in males and females.…”

Section: Discussionsupporting

confidence: 69%

“…Fitzgerald et al (1989) showed a higher level of MDMA, but not the metabolite MDA, in the plasma of female rats after a single drug injection, whereas Chu et al (1996) reported lower brain concentrations of MDA, but not MDMA, in female rats after MDMA. Two recent behavioral studies report that females show enhanced locomotion, less startle response, and comparable effects in the plus maze Pelenicek et al 2005).…”

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confidence: 79%

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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“…Several studies suggest a non-linear pharmacokinetic response to MDMA in human, monkey and rat (Kolbrich et al, 2008;de la Torre et al, 2000;Chu et al, 1996;Mueller et al, 2008). There have been a few reports regarding the physical or pharmacological effects resulting from interactions caused by MDMA tablet intake or multi-drug abuse.…”

Section: Pharmacodynamic Effects Of Mdma On Dopamine and 5-ht Levels mentioning

confidence: 99%

Pharmacodynamic interactions between MDMA and concomitants in MDMA tablets on extracellular dopamine and serotonin in the rat brain

Ikeda

Igari

Fuchigami

et al. 2011

European Journal of Pharmacology

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Baseline levels of dopamine and 5-HT in the striatum were 16.5±7.7 and 3.5±1.7 nM (mean ± standard deviation), respectively. After a single administration of MDMA (10 mg/kg, i.p.), a dramatic increase in extracellular dopamine (C max : 36.1-fold vs. baseline) and 5-HT levels (C max : 9.3-fold vs. baseline) was observed. When rats were co-administered with methamphetamine (1, 5 or 10 mg/kg) with MDMA, the dopamine levels induced by MDMA increased in a methamphetamine-dose-dependent manner (C max : 2.5-, 3.5-, and 3.8-fold vs. MDMA). A similar trend was observed in 5-HT levels (C max : 1.1-, 1.3-, and 1.8-fold vs. MDMA). In contrast, ketamine and caffeine showed synergistic effects on the monoamine levels induced by MDMA, whereas the individual administration of either of these compounds did not affect monoamine levels. Ketamine (1, 5 mg/kg) decreased the dopamine levels induced by MDMA (C max : 0.9-and 0.7-fold vs. MDMA) and increased the 5-HT levels induced by MDMA (C max : 1.4-and 1.6-fold vs. MDMA), and co-administration of caffeine (20 2 mg/kg) with MDMA increased dopamine levels (C max : 1.7-fold vs. MDMA). These results suggest that exposure to multiple drugs in addition to MDMA can have neurotoxic effects. 249 words

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Disposition of methylenedioxymethamphetamine and three metabolites in the brains of different rat strains and their possible roles in acute serotonin depletion

Cited by 134 publications

References 18 publications

In vivo Effects of Abused ‘Bath Salt’ Constituent 3,4-methylenedioxypyrovalerone (MDPV) in Mice: Drug Discrimination, Thermoregulation, and Locomotor Activity

In vivo Effects of Abused ‘Bath Salt’ Constituent 3,4-methylenedioxypyrovalerone (MDPV) in Mice: Drug Discrimination, Thermoregulation, and Locomotor Activity

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

Pharmacodynamic interactions between MDMA and concomitants in MDMA tablets on extracellular dopamine and serotonin in the rat brain

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