Methamphetamine induces a low dopamine transporter expressing state without altering the total number of peripheral immune cells

Methamphetamine 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.

Automated summary

Methamphetamine, a commonly abused psychostimulant, targets the dopamine transporter (DAT) and inhibits dopamine uptake while increasing dopamine release in the brain. It also affects peripheral immune cells expressing DAT, leading to impaired wound healing and increased susceptibility to infection. The study showed that methamphetamine treatment down-regulated DAT expression in innate and adaptive immune cells, without affecting their total numbers. Additionally, serum cytokine distributions were altered in methamphetamine-treated mice. These findings suggest that methamphetamine modulates peripheral immune responses by regulating DAT expression.