Amphetamine-related drugs neurotoxicity in humans and in experimental animals: Main mechanisms. (August 2017)

• Record Type: Journal Article
• Authors: Moratalla, Rosario; Khairnar, Amit; Simola, Nicola; Granado, Noelia; García-Montes, Jose Ruben; Porceddu, Pier Francesca; Tizabi, Yousef; Costa, Giulia; Morelli, Micaela
• Is Part Of: Progress in neurobiology. Volume 155(2017:Aug.)
• Page Start: 149
• Page End: 170
• Publication Date: 2017-08
• Subjects: Dopamine -- Ecstasy -- Methamphetamine -- METH -- 3, 4-Methylenedioxymethamphetamine -- MDMA -- Mouse -- Neurodegeneration -- Neuroinflammation neurotoxicity -- Non-human primate -- Rat; AC adenylyl cyclase -- AcbSh nucleus accumbens shell -- AcbC nucleus accumbens core -- cAMP cyclic adenosine monophosphate -- CNS central nervous system -- CPu caudate putamen -- CREB cAMP responsive element binding protein -- CSF cerebrospinal fluid -- CYP cytochrome P450 enzymes -- DA dopamine -- DAT DA transporter -- 5, 7-DHT 5, 7-dihydroxytryptamine -- l-DOPA 3, 4-dihydroxy-l-phenylalanine -- DOPAC 3, 4-dihydroxyphenylacetic acid -- DPCPX dipropylcyclopentylxanthine, adenosine A1 receptor antagonist -- ERK extracellular-signal-regulated kinase -- FDA Food and Drug Administration -- fMRI functional magnetic resonance imaging -- GBR12909 vanoxerine, antagonist of DAT -- GFAP glial fibrillary acidic protein -- GLU glutamate -- GSH glutathione -- HHMA 3, 4-dihydroxymethamphetamine -- 5-HIAA 5-hydroxyindoleacetic acid -- HPA hypothalamus–pituitary–adrenal axis -- 5-HT serotonin -- HVA homovanillic acid -- HPLC high-performance liquid chromatography -- JAK Janus kinase -- JNK c-Jun N-terminal kinases -- ICV intracerebroventricular -- IL interleukin -- Mac-1 macrophage-1 antigen -- MAO-B monoamine oxidase type B -- MAPK mitogen-activated protein kinase -- α-MeDA α-methyldopamine -- MDA 3, 4-methylenedioxyamphetamine -- MDMA 3, 4-methylenedioxymethamphetamine -- METH methamphetamine -- MK-801 dizocilpine, NMDA receptor antagonist -- MOR-1 μ opioid receptor -- a-MPT alpha-methyl-para-tyrosine -- MPTP 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine -- MRI magnetic resonance imaging -- NA noradrenaline -- NAC N-acetylcysteine -- NET NA transporter -- 7-NI 7-nitroindazole -- NMDA N-methyl-d-aspartate -- NO nitric oxide -- 3-NT 3-nitrotyrosine -- nNOS neuronal NO synthase -- 6-OHDA 6-hydroxydopamine -- PD Parkinson's disease -- PET positron emission tomography -- PKC protein kinase C -- ROS reactive oxygen species -- RNS reactive nitrogen species -- SCH23390 dopamine D1 receptor antagonist -- SERT 5-HT transporter -- SN substantia nigra -- SNc SN pars compacta -- SOD superoxide dismutase -- SPECT single photon emission computed tomography -- TH tyrosine hydroxylase -- TNF tumor necrosis factor -- VMAT2 vesicular monoamine transporter -- VTA ventral tegmental area; Neurobiology -- Periodicals; Neurology -- Periodicals; Neurology -- Periodicals; Neurobiologie -- Périodiques; 612.8
• DOI: 10.1016/j.pneurobio.2015.09.011
• Languages: English
• ISSNs: 0301-0082

Abstract

Highlights: MDMA 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. 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.