Affiliation:
1. Department of Neuroscience University of Florida College of Medicine Gainesville Florida USA
2. Department of Oral Biology University of Florida College of Dentistry Gainesville Florida USA
3. Emerging Pathogens Institute University of Florida Gainesville Florida USA
4. Center for Immunology and Transplantation University of Florida Gainesville Florida USA
5. Center for Translational Research in Neurodegenerative Disease University of Florida Gainesville Florida USA
Abstract
AbstractMethamphetamine is a widely abused psychostimulant and one of the main targets of dopamine transporter (DAT). Methamphetamine reduces DAT‐mediated dopamine uptake and stimulates dopamine efflux leading to increased synaptic dopamine levels many folds above baseline. Methamphetamine also targets DAT‐expressing peripheral immune cells, reduces wound healing and increases infection susceptibility. Peripheral immune cells such as myeloid cells, B cells and T cells express DAT. DAT activity on monocytes and macrophages exhibits immune suppressive properties via an autocrine paracrine mechanism, where deletion or inhibition of DAT activity increases inflammatory responses. In this study, utilizing a mouse model of daily single dose of methamphetamine administration, we investigated the impact of the drug on DAT expression in peripheral immune cells. We found in methamphetamine‐treated mice that DAT expression was down‐regulated in most of the innate and adaptive immune cells. Methamphetamine did not increase or decrease the total number of innate and adaptive immune cells but changed their immunophenotype to low‐DAT‐expressing phenotype. Moreover, serum cytokine distributions were altered in methamphetamine‐treated mice. Therefore, resembling its effect in the CNS, in the periphery, methamphetamine regulates DAT expression on peripheral immune cell subsets, potentially describing methamphetamine regulation of peripheral immunity.
Funder
National Center for Advancing Translational Sciences
National Institute of Neurological Disorders and Stroke
National Institute on Drug Abuse
Karen Toffler Charitable Trust
National Institute of Allergy and Infectious Diseases
Subject
Pharmacology,Toxicology,General Medicine
Cited by
4 articles.
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