Methamphetamine Activates Toll-Like Receptor 4 to Induce Central Immune Signaling within the Ventral Tegmental Area and Contributes to Extracellular Dopamine Increase in the Nucleus Accumbens Shell.

ABSTRACT: Methamphetamine (METH) is a globally abused, highly addictive stimulant. While investigations of the rewarding and motivational effects of METH have focused on neuronal actions, increasing evidence suggests that METH can also target microglia, the innate immune cells of the central nervous system, causing release of proinflammatory mediators and therefore amplifying the reward changes in the neuronal activity induced by METH. However, how METH induces neuroinflammatory responses within the central nervous system (CNS) is unknown. Herein, we provide direct evidence that METH creates neuroinflammation, at least in part, via the activation of the innate immune Toll-like receptor 4 (TLR4). Biophysical studies revealed that METH bound to MD-2, the key coreceptor of TLR4. Molecular dynamics simu

SUBMITTER: Wang X 

PROVIDER: S-EPMC8316980 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature