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

Article ID	Journal	Published Year	Pages	File Type
5739166	Progress in Neurobiology	2017	22 Pages	PDF

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.

Keywords

CREB 5-HT 6-OHDA Jnk CPU CyP GFAP GSH NAC 6-Hydroxydopamine ERK SNC RNS DAT ICV ACBC intracerebroventricular MPTP NMDA N-methyl-d-aspartate nNOS VTA DOPAC MK-801 5-HIAA DPCPX PKC MDMA AcbSh 7-NI SCH23390 MAO-B 3-NT VMAT2 GBR12909 MOR-1 FDA MDA Alpha-methyl-para-tyrosine Monoamine oxidase type B dopamine D1 receptor antagonist TNF Janus kinase 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 3-nitrotyrosine 3,4-Methylenedioxyamphetamine 3,4-methylenedioxymethamphetamine 3,4-dihydroxyphenylacetic acid 3,4-dihydroxy-l-phenylalanine 5-Hydroxyindoleacetic acid 5,7-DHT 5,7-dihydroxytryptamine 7-nitroindazole c-Jun N-terminal kinases cAMP l-DOPA MAPK N-acetylcysteine ROS μ Opioid receptor Cyclic adenosine monophosphate adenylyl cyclase Macrophage-1 antigen cytochrome P450 enzymes MRI Ecstasy interleukin SPECT Parkinson's disease Magnetic resonance imaging fMRI functional magnetic resonance imaging substantia nigra Neurodegeneration single photon emission computed tomography Positron emission tomography tyrosine hydroxylase Vesicular monoamine transporter 5-HT transporter DA transporter NET CNS Dopamine Food and Drug Administration SERT SOD Serotonin Superoxide dismutase central nervous system tumor necrosis factor Cerebrospinal fluid CSF METH Methamphetamine hypothalamus–pituitary–adrenal axis Mouse Rat Mac-1 HPA ventral tegmental area non-human primate noradrenaline Neuronal NO synthase Nitric oxide nucleus accumbens core nucleus accumbens shell homovanillic acid Caudate putamen PET cAMP responsive element binding protein Glial fibrillary acidic protein Protein kinase C mitogen-activated protein kinase HVA JAK HPLC high-performance liquid chromatography extracellular-signal-regulated kinase Glu Glutathione glutamate reactive nitrogen species Reactive oxygen species