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Published on: February 18, 2016
Methamphetamine sensitization attenuates the febrile and neuroinflammatory response to a subsequent peripheral immune
J B Buchanan1, N L Sparkman, R W Johnson
1Laboratory of Integrative Immunology and Behavior, Department of Animal Sciences, University of Illinois Urbana-Champaign, 1207 W. Gregory Drive, Urbana, IL 61801, USA. jessieb@illinois.edu
Abstract:
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 sensitization, a model of stimulant psychosis and an indicator of drug addiction, would interfere with the thermoregulatory and neuroinflammatory response to a subsequent peripheral immune stimulus. C57BL6/J mice were given either 1 mg/kg MA or saline i.p. once a day for 5 days to produce behavioral sensitization. Seventy-two hours following the last MA injection, 100 microg/kg LPS or saline was co-administered with 1 mg/kg MA or saline and blood and brains were collected. Here we report that while co-administration of LPS and MA did not affect the LPS-induced increase in central cytokine mRNA, mice sensitized to MA showed an attenuated central response to LPS. Interestingly, the peripheral response to LPS was not affected by MA sensitization. Plasma cytokines increased similarly in all groups after LPS. Further, c-Fos expression in the nucleus of the solitary tract did not differ between groups, suggesting that the periphery-to-brain immune signal is intact in MA-sensitized mice and that the deficit lies in the central cytokine compartment. We also show that MA sensitization decreased LPS- or acute MA-induced microglial Iba1 expression compared to non-sensitized mice. Taken together, these data show that MA sensitization interferes with the normal central immune response, preventing the CNS from efficiently responding to signals from the peripheral immune system.
Insights
Methamphetamine (MA) sensitization impairs the central nervous system's immune response to peripheral signals. This neuroinflammation interference prevents the brain from efficiently responding to immune system challenges in addiction models.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Methamphetamine (MA) use activates microglia and can cause neurotoxicity.
- MA use is linked to neuroinflammation, impacting the brain's immune environment.
- MA sensitization models stimulant psychosis and drug addiction.
Purpose of the Study:
- To investigate if MA sensitization affects thermoregulatory and neuroinflammatory responses to peripheral immune stimuli.
- To determine how MA sensitization alters the central nervous system's reaction to immune challenges.
Main Methods:
- C57BL6/J mice received daily MA or saline injections for 5 days to induce behavioral sensitization.
- Seventy-two hours post-MA, mice were co-administered lipopolysaccharide (LPS) or saline with MA or saline.
- Blood and brain samples were collected to analyze cytokine mRNA, c-Fos expression, and microglial Iba1 expression.
Main Results:
- MA sensitization attenuated the central neuroinflammatory response to LPS, while peripheral responses remained unaffected.
- Plasma cytokine levels increased similarly across groups after LPS administration.
- MA sensitization reduced LPS- or acute MA-induced microglial Iba1 expression, indicating altered microglial activation.
Conclusions:
- Methamphetamine sensitization interferes with the central immune response to peripheral immune system signals.
- The deficit in immune response lies within the central cytokine compartment, not in the periphery-to-brain signaling.
- MA sensitization prevents the central nervous system from efficiently responding to peripheral immune challenges.
