Dissociation between hypothermia and neurotoxicity caused by mephedrone and methcathinone in TPH2 knockout mice

Anneken, John H.; Angoa‐Pérez, Mariana; Sati, Girish C.; Crich, David; Kuhn, Donald M.

doi:10.1007/s00213-018-4991-8

Cited by 6 publications

(2 citation statements)

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“…The rationale for this experiment was the observation that while both METH and 4-MMC produce hyperthermia, 4-MMC has also been reported to produce a brief hypothermic response. However, they reported that although the knockout mice did not experience the characteristics hypothermic response, no increase in toxicity was observed in the knockouts vs. the wild-types ( Anneken et al, 2019 ). Another possibility is that 4-MMC has a different effect of mitochondria than METH, which has been associated with mitochondrial-dependent mechanisms of toxicity ( Shin et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…This raises the question as to what pharmacological differences between 4-MMC and METH result in the latter much more readily inducing neurotoxicity in animal models. Anneken et al (2018) hypothesized that the proposed difference could be due to differences in how METH and 4-MMC access the drug-releasable pool of DA. However, their experiments showed that combining the drugs with L-DOPA, which increases the size of the release pool, did in fact not precipitate any 4-MMC neurotoxicity while enhancing the toxic effects of METH.…”

Section: Discussionmentioning

confidence: 99%

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Alcohol Co-Administration Changes Mephedrone-Induced Alterations of Neuronal Activity

et al. 2021

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Mephedrone (4-MMC), despite its illegal status, is still a widely used psychoactive substance. Its effects closely mimic those of the classical stimulant drug methamphetamine (METH). Recent research suggests that unlike METH, 4-MMC is not neurotoxic on its own. However, the neurotoxic effects of 4-MMC may be precipitated under certain circumstances, such as administration at high ambient temperatures. Common use of 4-MMC in conjunction with alcohol raises the question whether this co-consumption could also precipitate neurotoxicity. A total of six groups of adolescent rats were treated twice daily for four consecutive days with vehicle, METH (5 mg/kg) or 4-MMC (30 mg/kg), with or without ethanol (1.5 g/kg). To investigate persistent delayed effects of the administrations at two weeks after the final treatments, manganese-enhanced magnetic resonance imaging brain scans were performed. Following the scans, brains were collected for Golgi staining and spine analysis. 4-MMC alone had only subtle effects on neuronal activity. When administered with ethanol, it produced a widespread pattern of deactivation, similar to what was seen with METH-treated rats. These effects were most profound in brain regions which are known to have high dopamine and serotonin activities including hippocampus, nucleus accumbens and caudate-putamen. In the regions showing the strongest activation changes, no morphological changes were observed in spine analysis. By itself 4-MMC showed few long-term effects. However, when co-administered with ethanol, the apparent functional adaptations were profound and comparable to those of neurotoxic METH.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Alcohol Co-Administration Changes Mephedrone-Induced Alterations of Neuronal Activity

et al. 2021

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Methcathinone and 3-Fluoromethcathinone Stimulate Spontaneous Horizontal Locomotor Activity in Mice and Elevate Extracellular Dopamine and Serotonin Levels in the Mouse Striatum

et al. 2018

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Methcathinone (MC) and 3-fluoromethcathinone (3-FMC) are well-known members of the synthetic cathinone derivatives, the second most abused group of novel psychoactive substances (NPS). They are considered as methamphetamine-like cathinones, as they elicit their psychostimulatory effects via inhibition of monoamine uptake and enhanced release. The present study examines the effects of MC and 3-FMC on the spontaneous locomotor activity of mice and extracellular levels of dopamine and serotonin in the mouse striatum. Both MC and 3-FMC produced a dose-dependent increase of horizontal locomotor activity, but no significant changes in rearing behavior were observed. The locomotor stimulation induced by MC and 3-FMC is mediated by activation of dopaminergic neurotransmission, as selective D1-dopamine receptor antagonist, SCH 23390, abolished the effects of both drugs. In line with pharmacological data obtained by previous in vitro studies, MC and 3-FMC produced potent increases of extracellular dopamine and serotonin levels in the mouse striatum. Taken together, results presented within this study confirm previous findings and expand our knowledge on the pharmacology of MC and 3-FMC along with their behavioral effects.

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The pharmacology and neurotoxicology of synthetic cathinones

Angoa-Perez,

Kuhn

2024

Advances in Pharmacology

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Dissociation between hypothermia and neurotoxicity caused by mephedrone and methcathinone in TPH2 knockout mice

Cited by 6 publications

References 44 publications

Alcohol Co-Administration Changes Mephedrone-Induced Alterations of Neuronal Activity

Alcohol Co-Administration Changes Mephedrone-Induced Alterations of Neuronal Activity

Methcathinone and 3-Fluoromethcathinone Stimulate Spontaneous Horizontal Locomotor Activity in Mice and Elevate Extracellular Dopamine and Serotonin Levels in the Mouse Striatum

The pharmacology and neurotoxicology of synthetic cathinones

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