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

Abstract

Abstract 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. Copyright © 2015. Published by Elsevier Ltd. ; This work was supported by grants from the Spanish Ministerios de Economía y Competitividad (SAF2013-48532-R) and of Sanidad Política Social e Igualdad(PNSD #2012/071, and ISCIII, CIBERNED CB06/05/0055) and Comunidad de Madrid ref. S2011/BMD-2336 to RM and by funds from the Regione Autonoma della Sardegna (Legge Regionale 7 Agosto 2007, N.7, annualità 2008 and 2010) to MM and by funds from to Sardinian Regional Government for financial support (P.O.R. Sardegna F.S.E. Operational Programme of the Autonomous Region of Sardinia, European Social Fund 2007–2013 – Axis IV Human Resources, Objective l.3, Line of Activity l.3.1 "Avviso di chiamata per il finanziamento di Assegni di Ricerca") to. NS. ; Peer Reviewed