Behavioural analysis of the acute and chronic effects of MDMA treatment in the rat

Marston, Hugh; Reid, M; Lawrence, Jane A.; Olverman, Henry J.; Butcher, Steven P.

doi:10.1007/s002130050978

Cited by 98 publications

(98 citation statements)

References 29 publications

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“…The temperature results agree with previous observations that MDMA increases body temperature (Colado et al 1993;Dafters 1994;Mechan et al 2001) and that this response diminishes across repeated days of administration (Cassel et al 2004;Marston et al 1999;Slikker et al 1989). Locomotor activity has been reported to decrease or not change after comparable regimens (Cassel et al 2004;Marston et al 1999;Slikker et al 1989). Effects on locomotion likely reflect the specific dose regimen.…”

Section: Discussionsupporting

confidence: 91%

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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Section: Discussionsupporting

confidence: 91%

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

et al. 2006

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“…Rats given neurotoxic doses of MDMA were mildly impaired in developing efficient search strategies in a place navigation task (Robinson et al, 1993). MDMA also produced deficits in a delayed non-match-to-place task in rats (Marston et al, 1999). Morley et al (2001) report that rats exposed to high (but not low) doses of MDMA showed impairments on the novelty preference OR task.…”

Section: Discussionmentioning

confidence: 99%

Impaired Object Recognition Memory Following Methamphetamine, but not p-Chloroamphetamine- or d-Amphetamine-Induced Neurotoxicity

Belcher

O’Dell

Marshall

2005

Neuropsychopharmacol

106

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Repeated moderate doses of methamphetamine (mAMPH) damage forebrain monoaminergic terminals and nonmonoaminergic cells in somatosensory cortex, and impair performance in a novelty preference task of object recognition (OR). This study aimed to determine whether the memory deficit seen after a neurotoxic mAMPH regimen results from damage to dopamine (DA) and/or serotonin (5-HT) terminals. Animals were given a neurotoxic regimen of mAMPH, p-chloroamphetamine (PCA, preferentially damages 5-HT terminals), damphetamine (d-AMPH, preferentially damages DA terminals), or saline. After 1 week, animals were trained and tested for OR memory. Rats treated with mAMPH showed no recognition memory during the short-term memory (STM) test, whereas both PCA-and d-AMPH-treated rats showed OR STM scores comparable to controls. After behavioral testing, the specificity of monoaminergic lesions was determined by postmortem [ 125 I]RTI-55 binding to dopamine (DAT) and serotonin (SERT) transporter proteins. Tissue from a separate group of animals killed 3 days after drug treatment was processed for Fluoro-Jade (F-J) fluorescence histochemistry to detect damaged cortical neurons. mAMPH-treated rats showed reductions in striatal DAT and hippocampal (HC) and perirhinal (pRh) SERT, as well as degeneration of neurons in primary somatosensory cortex. In PCA-treated rats, HC and pRh SERT were substantially depleted, but striatal DAT and cortical neuron survival were unaffected. By contrast, d-AMPH-treated animals showed marked depletions in striatal DAT and cortical neurodegeneration, but HC and pRh SERT were unaffected. This pattern of results indicates that no single feature of mAMPH-induced neurotoxicity is sufficient to produce the OR impairments seen after mAMPH treatment.

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“…Prevention of hyperthermia, however, was observed only after the first treatment, as in the present experiment. This limited prevention might have resulted from: (1) tolerance to the hyperthermic effects of MDMA (Marston et al, 1999) or (2) tolerance to the effect of ethanol, perhaps specifically in the presence of MDMA. The pharmacokinetic and/or pharmacodynamic mechanisms underlying these ethanol-induced effects remain as yet unknown.…”

Section: Acute Effects Of Etoh And/or Mdma Intoxicationsmentioning

confidence: 99%

“…Beside hyperlocomotion and hyperthermia, MDMA alters motor coordination (Marston et al, 1999), anxiety (Bhattacharya et al, 1998;Morley and McGregor, 2000;Sumnall et al, 2004), and cognitive functions (Braida et al, 2002;Ho et al, 2004;Marston et al, 1999; but see Ricaurte et al, 1993). With exception of the effects described by Cassel et al (2004;see also Rezvani et al, 1992), the acute behavioral effects of both drugs in combination were not studied yet in animals.…”

Section: Long-term Effects Of Etoh And/or Mdma On Behaviormentioning

confidence: 99%

Ethanol, 3,4-Methylenedioxymethamphetamine (Ecstasy) and Their Combination: Long-Term Behavioral, Neurochemical and Neuropharmacological Effects in the Rat

Cassel

Riegert

Rutz³

et al. 2005

Neuropsychopharmacol

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This study investigated long-term behavioral, neurochemical, and neuropharmacological effects of ethanol-(7)-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) combinations. Over 4 consecutive days, male Long-Evans rats received 1.5 g/kg ethanol and/or 10 mg/kg MDMA, or saline. Rectal temperatures were taken in some rats. Starting 4 days after the last injection, we tested working memory, sensory-motor coordination, and anxiety. Subsequently, we measured cortical, striatal, septal, and hippocampal monoamines (last MDMA injection-euthanasia delay: 20 days), or electrically evoked release of serotonin (5-HT) in cortical and hippocampal slices, and its modulation in the presence of CP 93,129 (3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrollo[3,2-b]pyrid-5-one) or methiotepin (last MDMA injection-euthanasia delays: 3-6 weeks). Ethanol attenuated the MDMA-induced hyperthermia, but only on the first day. In the longterm, MDMA reduced 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) content in most brain regions. The behavioral and neurochemical effects of the ethanol-MDMA combination were comparable to those of MDMA alone; sensory-motor coordination was altered after ethanol and/or MDMA. In hippocampal slices from rats given ethanol and MDMA, the CP 93,129-induced inhibition and methiotepininduced facilitation of 5-HT release were stronger and weaker, respectively, than in the other groups. This is the first study addressing long-term effects of repeated MDMA and EtOH combined treatments in experimental animals. Whereas the drug combination produced the same behavioral and neurochemical effects as MDMA alone, our neuropharmacological results suggest that MDMA-EtOH interactions may have specific long-term consequences on presynaptic modulation of hippocampal 5-HT release, but not necessarily related to MDMA-induced depletion of 5-HT. Thus, it is likely that the psycho(patho)logical problems reported by ecstasy users drinking alcohol are not solely due to the consumption of MDMA.

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Behavioural analysis of the acute and chronic effects of MDMA treatment in the rat

Cited by 98 publications

References 29 publications

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

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

Impaired Object Recognition Memory Following Methamphetamine, but not p-Chloroamphetamine- or d-Amphetamine-Induced Neurotoxicity

Ethanol, 3,4-Methylenedioxymethamphetamine (Ecstasy) and Their Combination: Long-Term Behavioral, Neurochemical and Neuropharmacological Effects in the Rat

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