[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-291827-105":59,"doc-detail-291827-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","the-sigma-1-receptor-modulates-methamphetamine-dysregulation-of-dopamine-neurotransmission","The sigma-1 receptor modulates methamphetamine dysregulation of dopamine neurotransmission","","The work investigates how the sigma-1 receptor (σ1R) influences methamphetamine-driven disruption of dopamine signaling. Methamphetamine normally increases extracellular dopamine via dopamine transporter (DAT)-dependent mechanisms and elevates neuronal firing, reward-related behaviors, and locomotion. The study shows that σ1R activation blocks DAT-mediated increases in dopaminergic neuron firing, reduces methamphetamine-stimulated dopamine efflux without altering basal signaling, and dampens drug-evoked behavioral and reward responses. Mechanistically, σ1R is found to interact with DAT near the plasma membrane and attenuate methamphetamine-induced Ca2+ signaling, supporting σ1R as a treatment target.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/the-sigma-1-receptor-modulates-methamphetamine-dysregulation-of-dopamine-neurotransmission/291827/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/the-sigma-1-receptor-modulates-methamphetamine-dysregulation-of-dopamine-neurotransmission/291827.png","ImageObject",300,407,{"name":92,"@type":93},"Felix Montgomery","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-04","2026-09-17",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",14,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"How does methamphetamine dysregulate dopamine neurotransmission?","Question",{"text":113,"@type":114},"Methamphetamine increases extracellular dopamine through DAT-dependent processes and enhances dopaminergic neuron excitability, driving rewarding and addictive effects.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What effect does σ1R activation have on methamphetamine-induced neuronal firing?",{"text":118,"@type":114},"σ1R activation prevents methamphetamine-induced, DAT-mediated increases in the firing activity of dopamine neurons.",{"name":120,"@type":111,"acceptedAnswer":121},"Does σ1R activation change basal dopamine neurotransmission?",{"text":122,"@type":114},"In vitro and in vivo measurements show σ1R activation decreases methamphetamine-stimulated dopamine efflux without affecting basal dopamine neurotransmission.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},291827,1789647019,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":130,"read_time":145,"preview_page_count":4},549768064778,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","ARTICLE  \n DOI: 10.1038/s41467-017-02087-x  OPEN  \nThe sigma-1 receptor modulates methamphetamine dysregulation of dopamine neurotransmission  \nDanielle O. Sambo1, Min Lin1, Anthony Owens2, Joseph J. Lebowitz1, Ben Richardson  1, Darin A. Jagnarine3, Madhur Shetty4, Meghan Rodriquez4, Taiwo Alonge1, Mishaal Ali1, Jonathan Katz  5, Long Yan6,  \nMarcelo Febo3, L. Keith Henry4, Adriaan W. Bruijnzeel3, Lynette Daws2 & Habibeh Khoshbouei1  \nDopamine neurotransmission is highly dysregulated by the psychostimulant methamphetamine, a substrate for the dopamine transporter (DAT) . Through interactions with DAT, methamphetamine increases extracellular dopamine levels in the brain, leading to its rewarding and addictive properties. Methamphetamine also interacts with the sigma-1 receptor (σ1 R), an inter-organelle signaling modulator. Using complementary strategies, weidentified a novel mechanism for σ1 R regulation of dopamine neurotransmission in response to methamphetamine. We found that σ1 R activation prevents methamphetamine-induced, DAT-mediated increases in firing activity of dopamine neurons. In vitro and in vivo amperometric measurements revealed that σ1 R activation decreases methamphetaminestimulated dopamine efflux without affecting basal dopamine neurotransmission. Consistent with these findings, σ1 R activation decreases methamphetamine-induced locomotion, motivated behavior, and enhancement of brain reward function. Notably, we revealed that the σ1 R interacts with DAT at or near the plasma membrane and decreases methamphetamineinduced Ca2+ signaling, providing potential mechanisms. Broadly, these data provide evidence for σ1 R regulation of dopamine neurotransmission and support the σ1 R as a putative target for the treatment of methamphetamine addiction.  \n1 Department of Neuroscience, University of Florida, Gainesville, FL 32611, USA. 2 Department of Cellular & Integrative Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. 3 Department of Psychiatry, University of Florida, Gainesville, FL 32611, USA. 4 Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203, USA. 5 Psychobiology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. 6 Max Plank Institute for Neuroscience Jupiter, Jupiter, FL 33458, USA.  \nCorrespondence and requests for materials should be addressed to H. K. (email: Habibeh@ufl . edu)  \nNATURE COMMUNICATIONS |8: 2228 |DOI: [10.1038/s41467-017-02087-x](10.1038/s41467-017-02087-x |www.nature.com/naturecommunications)[ |](10.1038/s41467-017-02087-x |www.nature.com/naturecommunications)[www.nature.com/naturecommunications](10.1038/s41467-017-02087-x |www.nature.com/naturecommunications) 1  \nThe dopamine transporter (DAT) is a transmembrane  \nprotein implicated in multiple physiological and patholo  \ngical conditions, including movement, reward, and drug addiction 1. DAT facilitates the uptake of dopamine from the extracellular fluid back into the neuron and modulates the excitability of dopaminergic neurons, making it a crucial regulator of dopamine homeostasis in the brain 1,2. DAT is also the primary target for the psychostimulants cocaine and methamphetamine (METH)3,4. The reinforcing effects and abuse potential of these psychostimulants directly correlate with their ability to increase extracellular dopamine levels in brain, albeit via different mechanisms3. Whereas cocaine increases extracellular  \ndopamine by blocking DAT, METH increases extracellular dopamine levels by at least three well-described mechanisms: (1) competitive inhibition of dopamine uptake, (2) stimulation of dopamine efflux, and (3) internalization of DAT from the plasma membrane5–8. Furthermore, METH also increases the excitability of dopaminergic neurons in a DAT-dependent fashion2,9, 10. Thenet result of these actions is a robust increase in extracellular dopamine levels in brain. Currentl","cbCaiq2FQpEaerTi","https://ap.wps.com/l/cbCaiq2FQpEaerTi","pdf",2479852,18,"English","# Article Overview\n## Methamphetamine and DAT-mediated dopamine dysregulation\n## Sigma-1 receptor modulation: cellular findings\n## Behavioral and reward-related outcomes\n## Proposed mechanism at or near the plasma membrane","[{\"question\":\"How does methamphetamine dysregulate dopamine neurotransmission?\",\"answer\":\"Methamphetamine increases extracellular dopamine through DAT-dependent processes and enhances dopaminergic neuron excitability, driving rewarding and addictive effects.\"},{\"question\":\"What effect does σ1R activation have on methamphetamine-induced neuronal firing?\",\"answer\":\"σ1R activation prevents methamphetamine-induced, DAT-mediated increases in the firing activity of dopamine neurons.\"},{\"question\":\"Does σ1R activation change basal dopamine neurotransmission?\",\"answer\":\"In vitro and in vivo measurements show σ1R activation decreases methamphetamine-stimulated dopamine efflux without affecting basal dopamine neurotransmission.\"}]","The sigma-1 receptor modulates methamphetamine dysregulation of dopamine neurotransmission | PDF",45]