Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8536828 | Pharmacology & Therapeutics | 2018 | 16 Pages |
Abstract
Methamphetamine (METH) abuse is a major public health issue around the world, yet there are currently no effective pharmacotherapies for the treatment of METH addiction. METH is a potent psychostimulant that increases extracellular dopamine levels by targeting the dopamine transporter (DAT) and alters neuronal activity in the reward centers of the brain. One promising therapeutic target for the treatment of METH addiction is the sigma-1 receptor (Ï1R). The Ï1R is an endoplasmic reticulum-localized chaperone protein that is activated by cellular stress, and, unique to this chaperone, its function can also be induced or inhibited by different ligands. Upon activation of this unique “chaperone receptor”, the Ï1R regulates a variety of cellular functions and possesses neuroprotective activity in the brain. Interestingly, a variety of Ï1R ligands modulate dopamine neurotransmission and reduce the behavioral effects of METH in animal models of addictive behavior, suggesting that the Ï1R may be a viable therapeutic target for the treatment of METH addiction. In this review, we provide background on METH and the Ï1R as well as a literature review regarding the role of Ï1Rs in modulating both dopamine neurotransmission and the effects of METH. We aim to highlight the complexities of Ï1R pharmacology and function as well as the therapeutic potential of the Ï1R as a target for the treatment of METH addiction.
Keywords
CPPMS-377BMY 14802NE-1001,3-di-o-tolylguanidineσ1RSA4503BD1063VMAT2PRE-084ATSMDMAPKCVTAAMPHN-methyl-d-aspartatePCPDTGNMDADATDMTBiPN,N-dimethyltryptamineAmphetamineDopamine transporterParkinson's diseaseconditioned place preferencesubstantia nigraDopaminePhencyclidineMETHMethamphetamineAmphetamine-type stimulantsVesicular monoamine transporter-2ventral tegmental areaBinding immunoglobulin ProteinProtein kinase CSigma-2 receptorSigma-1 receptor
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Authors
Danielle O. Sambo, Joseph J. Lebowitz, Habibeh Khoshbouei,