Locomotor and pyretic effects of MDMA–ethanol associations in rats

Cassel, Jean‐Christophe; Jeltsch, Hélène; Koenig, Julie; Jones, Byron C.

doi:10.1016/j.alcohol.2004.09.003

Cited by 28 publications

(39 citation statements)

References 14 publications

(22 reference statements)

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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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“…In mice given ethanol and MDMA, the striatal concentration of MDMA was about four times larger than in controls, suggesting that ethanol may interfere with (i) MDMA metabolism, (ii) penetration of MDMA into the brain, or (iii) removal of MDMA from the brain (Johnson et al, 2004). Should the same be true in rats, and as the effects of ethanol on the locomotor (Cassel et al, 2004); (see also Rezvani et al, 1992) and pyretic consequences of MDMA were in opposite directions, one pharmacokinetic explanation could be that MDMA (or a particular metabolite) was involved in one of the effects (hyperlocomotion), while a metabolite (or a further metabolite) would be involved in the other one (hyperthermia). Dissociation between the effects of MDMA and its metabolites has not been demonstrated for behavioral or physiological variables, but were described for toxicity vs 5-HT release.…”

Section: Acute Effects Of Etoh And/or Mdma Intoxicationsmentioning

confidence: 94%

“…On four occasions, 24 h apart, rats were treated with one of the drugs/combination. The acute pyretic and locomotor responses to these drugs and to their combination have been considered in a recent experiment (Cassel et al, 2004), and were not assessed in the present study, except for body temperature on a randomly selected series of rats (see below).…”

Section: Drugs and Treatment Protocolsmentioning

confidence: 99%

“…We recently reported that MDMA-induced hyperactivity and hyperthermia (Cassel et al, 2004) did not change in magnitude when the treatment was repeated at three other occasions, 24 h apart. Furthermore, ethanol treatment had no effect on activity scores, but resulted in a small but significant hypothermia (about À0.51C) that showed some tolerance on subsequent days.…”

Section: Acute Effects Of Etoh And/or Mdma Intoxicationsmentioning

confidence: 99%

“…In a recent series of experiments in rats (Cassel et al, 2004), we found that ethanol dramatically potentiated MDMA-induced hyperlocomotor effect. In contrast, ethanol prevented the hyperpyretic effect of MDMA, at least acutely.…”

Section: Introductionmentioning

confidence: 99%

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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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Effect of the combination of mephedrone plus ethanol on serotonin and dopamine release in the nucleus accumbens and medial prefrontal cortex of awake rats

López-Arnau

Buenrostro-Jáuregui

Camarasa

et al. 2018

Naunyn-Schmiedeberg's Arch Pharmacol

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Cathinones, such as mephedrone (Meph), are often co-abused with alcoholic drinks. In the present study, we investigated the combined effects of Meph plus ethanol (EtOH) on neurotransmitter release in the nucleus accumbens (NAc) and the medial prefrontal cortex (mPFC). A guide canula was stereotaxically implanted into either the NAc or the mPFC of male Sprague-Dawley rats. Seven days after surgery, a microdialysis probe was inserted and rats were administered saline, EtOH (1 g/kg, i.p.), Meph (25 mg/kg, s.c.), or their combination, and dialysates were collected. Serotonin (5-HT), dopamine (DA), and their metabolites (5-HIAA, DOPAC and HVA) were determined through high-pressure liquid chromatography coupled to mass spectrometry. 5-HT and DA peaked 40 min after Meph administration (with or without EtOH co-treatment) in both areas. EtOH combined with Meph increased the 5-HT release compared with the rats receiving Meph alone (85% in NAc, 65% in mPFC), although the overall change in the area under the curve only reached statistical significance in the NAc. In mPFC, the increased release of 5-HT lasted longer in the combination than that in the Meph group. Moreover, EtOH potentiated the psychostimulant effect of Meph measured as a locomotor activity. Given that both 5-HT and DA are also related with reward and impulsivity, the observed effects point to an increased risk of abuse liability when combining Meph with EtOH compared with consuming these drugs alone.

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Locomotor and pyretic effects of MDMA–ethanol associations in rats

Cited by 28 publications

References 14 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

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

Effect of the combination of mephedrone plus ethanol on serotonin and dopamine release in the nucleus accumbens and medial prefrontal cortex of awake rats

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