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.

Applied Neuroscience Research Group CEITEC Central European Institute of Technology Masaryk University Brno Czech Republic

Department of Biomedical Sciences Section of Neuropsychopharmacology University of Cagliari Via Ospedale 72 09124 Cagliari Italy

Department of Biomedical Sciences Section of Neuropsychopharmacology University of Cagliari Via Ospedale 72 09124 Cagliari Italy; Centre of Excellence for Neurobiology of Dependence University of Cagliari Cagliari Italy; National Research Council Institute of Neuroscience Cagliari Italy

Department of Pharmacology Howard University College of Medicine Washington DC USA

Instituto Cajal Consejo Superior de Investigaciones Científicas CSIC Madrid Spain; CIBERNED ISCIII Madrid Spain

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