Amphetamine-related drugs neurotoxicity in humans and in experimental animals: Main mechanisms

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HIGHLIGHTSMDMA damages serotonergic system in primates and rats and dopaminergic system in mice.METH damages the dopaminergic system in all animal species including humans.The nigrostriatal system is more vulnerable than the mesolimbic system.Within the striatum the striosomes are more vulnerable than the matrix.METH kills dopamine neurons as demonstrated by silver-staining in rodents.METH reduces DAT binding sites and motor skills in human addicts.Amphetamine-related drugs, such as 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (METH), are popular recreational psychostimulants. Several preclinical studies have demonstrated that, besides having the potential for abuse, amphetamine-related drugs may also elicit neurotoxic and neuroinflammatory effects. The neurotoxic potentials of MDMA and METH to dopaminergic and serotonergic neurons have been clearly demonstrated in both rodents and non-human primates. This review summarizes the species-specific cellular and molecular mechanisms involved in MDMA and METH-mediated neurotoxic and neuroinflammatory effects, along with the most important behavioral changes elicited by these substances in experimental animals and humans. Emphasis is placed on the neuropsychological and neurological consequences associated with the neuronal damage. Moreover, we point out the gap in our knowledge and the need for developing appropriate therapeutic strategies to manage the neurological problems associated with amphetamine-related drug abuse.

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