It is a feature described for 5-HT systems when administered to administration route or ambient temperature

Nevertheless, the studies did not extent the evaluation of DA to brain areas other than striatum or were performed with a drug exposure schedule not adjusted to mephedrone pharmacokinetics. The aim of this paper was to investigate the neurotoxicity profile of mephedrone in mice, addressing some of the limitations in the literature. Most authors described the neurotoxic effects of methamphetamine three days after exposition and those of MDMA seven days after. We examined the neurotoxic injury induced by mephedrone at 3 and 7 days after finishing the exposition. Obtaining as much mechanistic information as possible regarding mephedrone, as well as on its neurotoxic effects, is of the essence. In this regard, we have evaluated the in vivo effect of this cathinone following different dosage schedule whilst complementing it by performing in vitro experiments. With regards to MDMA, it is described that the magnitude of the acute hyperthermic response plays a major role in determining the severity of the consequences of its misuse, in such a way that ingesting the drug in hot, crowded dance club conditions, increases the possibility of subsequent cerebral neurotoxic effects. To simulate these usual conditions of drug exposure, the neurotoxicity studies with amphetamine-derivatives are usually performed at elevated ambient temperatures. Accordingly, present experiments were carried out at high room temperatures. This condition was not considered in previous published papers. In the present study we used adolescent mice, a feature that correlates with young adult consumers. We demonstrate that mephedrone induces an injury at nerve endings in the frontal cortex at a schedule of drug exposure that mimics human “weekend consumption”. The easy availability of cathinones and their initial status as legal highs may have contributed to their increasing popularity as drugs of abuse. Because of the relatively short history of the use of cathinones as recreational drugs, their effects among long-term users have yet to be determined. Based on its structural similarity to well established neurotoxic psychostimulants such as methamphetamine and MDMA, it was hypothesized that mephedrone would exert neuronal damage. However, there are important discrepancies concerning the neurotoxicity induced by cathinones. The inconsistent results could be attributed to differences in species, dosage. Some cases of aggressive behavior, even cannibalism, as a consequence of exposure to new designer drugs have been recently reported in the media. However, these cases have been poorly documented. In the present study, all mephedrone schedules induced the appearance of initial stereotypy consisting in repeated self-licking that was followed by aggressive behavior which leads to self-injuries. This is an especially important factor to be taken into account, seeing as it required animals to be housed individually.

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