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Current Neuropharmacology
ISSN (Print): 1570-159X
ISSN (Online): 1875-6190
VOLUME: 9
ISSUE: 1
DOI: 10.2174/157015911795016930









Role of Sigma Receptors in Methamphetamine-Induced Neurotoxicity

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Author(s): Nidhi Kaushal and Rae R. Matsumoto
Pages 54-57 (4)
Abstract:
Methamphetamine (METH) is a widely abused substance world over. Currently, there is no effective pharma- cotherapy to treat its effects. This necessitates identification of potential novel therapeutic targets. METH interacts with sigma (σ) receptors at physiologically relevant micromolar concentrations. In addition, σ receptors are present in organs like the brain, heart, and lungs at which METH acts. Additionally, σ receptors have been implicated in various acute and subchronic effects like locomotor stimulation, development of sensitization and neurotoxicity, where σ receptor antagonists attenuate these effects. σ Receptors may also have a role in METH-induced psychiatric complications such as depression, psychosis, cognitive and motor deficits. The neurotoxic effects of METH, which are cause for concern, can be prevented by σ receptor antagonists in mice. Mechanistically, METH-induced neurotoxicity involves factors like dopamine release, oxidative stress, endoplasmic reticulum stress, activation of mitochondrial death cascades, glutamate release, apoptosis, microglial activation, and hyperthermia. This review compiles studies from the literature that suggests an important role for σ receptors in many of the mechanisms of METH-induced neurotoxicity.
Keywords:
Methamphetamine, sigma receptors, oxidative stress, endoplasmic reticulum, mitochondria, neurotoxicity, dopamine, glutamate, opamine, Hperthermia, Psychosis, Depression, Protein Kinase, Apoptic Death Cell, ER Stress, Excitotoxicity
Affiliation:
Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, WV 26506, USA.