The combination of ethanol with mephedrone increases the signs of neurotoxicity and impairs neurogenesis and learning in adolescent CD-1 mice

Ciudad-Roberts, Andrés; Duart-Castells, Leticia; Camarasa, Jorge; Piccoli, David A.; Escubedo, Elena

doi:10.1016/j.taap.2015.12.019

Cited by 25 publications

(20 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The decrease in transporter level and enzyme markers points to an injury of the nerve endings (Escubedo et al 2005 ). It is postulated that mephedrone exerts its neurotoxic actions through oxidative stress which damages components of the cell membrane, nucleus, and mitochondria, leading to complete cell degradation (Ciudad-Roberts et al 2016 ).…”

Section: Introductionmentioning

confidence: 99%

The Effects of Exposure to Mephedrone During Adolescence on Brain Neurotransmission and Neurotoxicity in Adult Rats

et al. 2018

View full text Add to dashboard Cite

According to the European Drug Report (2016), the use of synthetic cathinones, such as mephedrone, among young people has rapidly increased in the last years. Studies in humans indicate that psychostimulant drug use in adolescence increases risk of drug abuse in adulthood. Mephedrone by its interaction with transporters for dopamine (DAT) and serotonin (SERT) stimulates their release to the synaptic cleft. In animal studies, high repeated doses of mephedrone given to adolescent but not adult mice or rats induced toxic changes in 5-hydroxytryptamine (5-HT) neurons. The aim of our study was to investigate the effects of mephedrone given in adolescence on brain neurotransmission and possible neuronal injury in adult rats. Adolescent male rats were given mephedrone (5 mg/kg) for 8 days. In vivo microdialysis in adult rats showed an increase in dopamine (DA), 5-HT, and glutamate release in the nucleus accumbens and frontal cortex but not in the striatum in response to challenge dose in animals pretreated with mephedrone in adolescence. The 5-HT and 5-hydroxyindoleacetic acid contents decreased in the striatum and nucleus accumbens while DA turnover rates were decreased in the striatum and nucleus accumbens. The oxidative damage of DNA assessed with the alkaline comet assay was found in the cortex of adult rats. Therefore, the administration of repeated low doses of mephedrone during adolescence does not seem to induce injury to 5-HT and DA neurons. The oxidative stress seems to be responsible for possible damage of cortical cell bodies which causes maladaptive changes in serotonergic and dopaminergic neurons.Electronic supplementary materialThe online version of this article (10.1007/s12640-018-9908-0) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%

The Effects of Exposure to Mephedrone During Adolescence on Brain Neurotransmission and Neurotoxicity in Adult Rats

et al. 2018

View full text Add to dashboard Cite

show abstract

“…For example, methylone (4 × 30 mg/kg at 2 hr intervals) can enhance putative damage to dopamine nerve endings as measured by decreases in DAT levels or binding more robustly in the presence of methamphetamine, yet oddly the same doses of MDPV appear to exert neuroprotective effects (Anneken et al 2015). More predictably, additive or synergistic neurotoxic effects have been shown when mephedrone is administered in combination with methamphetamine (Anneken et al 2018) or ethanol (Ciudad-Roberts et al 2016). Thus, there are highly complex mechanism of action of synthetic cathinones with regards to their ability to produce neurotoxic or monoamine-altering effects, and it is clear that such effects are dependent on a plethora of variables such, dose and frequency of administration, the presence of other drugs of abuse.…”

Section: Cellular Toxicity Induced By Synthetic Cathinonesmentioning

confidence: 99%

Cognitive deficits and neurotoxicity induced by synthetic cathinones: is there a role for neuroinflammation?

Leyrer‐Jackson

Nagy

2018

Psychopharmacology

View full text Add to dashboard Cite

Rationale.-The number of synthetic derivatives of cathinone, the primary psychoactive alkaloid found in Catha edulis (khat), has risen exponentially in the past decade. Synthetic cathinones (frequently referred to as "bath salts") produce adverse cognitive and behavioral sequelae, share similar pharmacological mechanisms of action with traditional psychostimulants, and may therefore trigger similar cellular events that give rise to neuroinflammation and neurotoxicity Objectives.-In this review, we provide a brief overview of synthetic cathinones, followed by a summary of cognitive deficits in animals and humans that have been documented following acute or repeated exposure. We also summarize growing evidence from in vitro and in vivo studies for synthetic cathinone-induced neurotoxicity, and provide a working hypothetic model of potential cellular mechanisms. Results.-Synthetic cathinones produce varying effects on markers of monoaminergic terminal function, and can increase the formation of reactive oxygen and nitrogen species, induce apoptotic signaling, and cause neurodegeneration and cytotoxicity. We hypothesize that these effects result from biochemical events similar to those induced by traditional psychostimulants. However, empirical evidence for the ability of synthetic cathinones to induce neuroinflammatory processes is currently lacking. Conclusions.-Like their traditional psychostimulant counterparts, synthetic cathinones appear to induce neurocognitive dysfunction and cytotoxicity, which are dependent on drug type, dose, frequency, and time following exposure. However, additional studies on synthetic cathinoneinduced neuroinflammation are clearly needed, as are investigations into the neurochemical and neuroimmune mechanisms underlying their neurotoxic effects. Such endeavors may lead to novel therapeutic avenues to promote recovery in habitual synthetic cathinone users.

show abstract

“…Despite the potentially added risks of mephedrone combined with alcohol, experimental data in humans about interactions between mephedrone and alcohol are very limited. Experimental studies in animal models concerning the effects induced after single and repeated mephedrone and alcohol administration, demonstrated that alcohol increases stimulant and rewarding effects of mephedrone (Ciudad-Roberts et al, 2015), and can also potentiate the neurotoxic properties of mephedrone in adolescent mice (Ciudad-Roberts et al, 2016). A recent study has concluded that mephedrone in combination with alcohol enhances the psychostimulant effect of mephedrone measured as locomotor activity.…”

Section: Introductionmentioning

confidence: 99%

Mephedrone and Alcohol Interactions in Humans

et al. 2020

View full text Add to dashboard Cite

Mephedrone (4-MMC, mephedrone) is a synthetic cathinone derivative included in the class of new psychoactive substances. It is commonly used simultaneously with alcohol (ethanol). The aim of the present study was to evaluate the interactions on subjective, cardiovascular and hormone effects and pharmacokinetics between mephedrone and alcohol in humans. Eleven male volunteers participated as outpatients in four experimental sessions in a double-blind, randomized, cross-over, and placebo-controlled clinical trial. Participants received a single oral dose of 200 mg of mephedrone plus 0.8 g/kg of alcohol (combination condition); 200 mg of mephedrone plus placebo alcohol (mephedrone condition); placebo mephedrone plus 0.8 g/kg of ethanol (alcohol condition); and placebo mephedrone plus placebo alcohol (placebo condition). Outcome variables included physiological (blood pressure, heart rate, temperature, and pupil diameter), psychomotor (Maddox wing), subjective (visual analogue scales, Addiction Research Center Inventory 49 item short form, and Valoración de los Efectos Subjetivos de Sustancias con Potencial de Abuso questionnaire), and pharmacokinetic parameters (mephedrone and ethanol concentrations). The study was registered in ClinicalTrials.gov, number NCT02294266. The mephedrone and alcohol combination produced an increase in the cardiovascular effects of mephedrone and induced a more intense feeling of euphoria and well-being in comparison to the two drugs alone. Mephedrone reduced the sedative effects produced by alcohol. These results are similar to those obtained when other psychostimulants such as amphetamines and 3,4methylenedioxymethamphetamine are combined simultaneously with alcohol. The abuse liability of mephedrone combined with alcohol is greater than that induced by mephedrone alone.

show abstract

The combination of ethanol with mephedrone increases the signs of neurotoxicity and impairs neurogenesis and learning in adolescent CD-1 mice

Cited by 25 publications

References 53 publications

The Effects of Exposure to Mephedrone During Adolescence on Brain Neurotransmission and Neurotoxicity in Adult Rats

The Effects of Exposure to Mephedrone During Adolescence on Brain Neurotransmission and Neurotoxicity in Adult Rats

Cognitive deficits and neurotoxicity induced by synthetic cathinones: is there a role for neuroinflammation?

Mephedrone and Alcohol Interactions in Humans

Contact Info

Product

Resources

About