A neurotoxic regimen of methamphetamine exacerbates the febrile and neuroinflammatory response to a subsequent peripheral immune stimulus

Methamphetamine (MA) use is associated with activation of microglia and, at high doses, can induce neurotoxicity. Given the changes in the neuroinflammatory environment associated with MA, we investigated whether MA administration would interfere with the thermoregulatory and neuroinflammatory response to a subsequent peripheral immune stimulus. C57BL6/J mice were given four i.p. injections of either 5 mg/kg MA or saline at two hour intervals. Twenty-four hours following the first MA injection, mice were given 100 μg/kg LPS or saline i.p. and blood and brains were collected. Here we report that mice exposed to MA developed higher fevers in response to LPS than did those given LPS alone. MA also exacerbated the LPS-induced increase in central cytokine mRNA. MA alone increased microglial Iba1 expression and expression was further increased when mice were exposed to both MA and LPS, suggesting that MA not only activated microglia but also influenced their response to a peripheral immune stimulus. Taken together, these data show that MA administration exacerbates the normal central immune response, most likely by altering microglia.