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. 2018 Jun 11:677:49-54.
doi: 10.1016/j.neulet.2018.04.037. Epub 2018 Apr 22.

The relationship between interleukin-6 and functional connectivity in methamphetamine users

Milky Kohno  1 , Jennifer M Loftis  2 , Marilyn Huckans  3 , Laura E Dennis  4 , Holly McCready  4 , William F Hoffman  5
Affiliations

The relationship between interleukin-6 and functional connectivity in methamphetamine users

Milky Kohno et al. Neurosci Lett. .

Abstract

Methamphetamine (MA) causes an increase in pro-inflammatory cytokines in animal models and in humans. Resulting activation of microglia and neuro-inflammation could, via effects on reward networks, mediate behavioral characteristics of addiction. We examined the relationship between interleukin-6 (IL-6) and corticolimbic and striatolimbic resting-state functional connectivity (RSFC). Thirty adults diagnosed with MA dependence and 20 control subjects underwent a resting-state functional magnetic resonance imaging (fMRI) scan and gave a blood sample for determination of plasma IL-6 levels. Seed-based RSFC analyses were performed to examine the interactive effect of group and IL-6 on ventral striatal and prefrontal connectivity. Within the MA group, IL-6 levels were positively related to striatolimbic RSFC but negatively related to corticostriatal RSFC. Our findings with IL-6 support the idea that inflammation may at least partly mediate the link among MA use disorder, RSFC, and behavior, possibly via effects on mesolimbic and mesocortical dopaminergic systems.

Keywords: Corticostriatal; IL-6; Inflammation; Mesocorticolimbic; Methamphetamine; Resting-state functional connectivity.

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Figures

Figure 1
Figure 1. Relationship between IL6 and parameter estimates of DLPFC and ventral striatal resting-state functional connectivity
A. RSFC with ventral striatal seed. Group x IL6 interaction, where MA users show greater positive relationship between IL6 and RSFC between ventral striatum, amygdala, hippocampus, insula, temporal and occipital cortices (p < 0.05, whole-brain corrected). B. RSFC with DLPFC seed. Group x IL6 interaction, where MA users show greater negative relationship between IL6 and RSFC between DLPFC, orbital frontal cortex, dorsal and ventral striatum and insula (p < 0.05, whole-brain corrected). Scatter plots show parameter estimates from significant functional clusters from the whole-brain regression of DLPFC and ventral striatum seed RSFC.
See this image and copyright information in PMC

References

    1. Clark KH, Wiley CA, Bradberry CW. Psychostimulant abuse and neuroinflammation: emerging evidence of their interconnection. Neurotox Res. 2013;23(2):174–88. - PubMed
    1. Goncalves J, Martins T, Ferreira R, Milhazes N, Borges F, Ribeiro CF, et al. Methamphetamine-induced early increase of IL-6 and TNF-alpha mRNA expression in the mouse brain. Ann N Y Acad Sci. 2008;1139:103–11. - PubMed
    1. LaVoie MJ, Card JP, Hastings TG. Microglial activation precedes dopamine terminal pathology in methamphetamine-induced neurotoxicity. Exp Neurol. 2004;187(1):47–57. - PubMed
    1. Loftis JM, Choi D, Hoffman W, Huckans MS. Methamphetamine causes persistent immune dysregulation: a cross-species, translational report. Neurotox Res. 2011;20(1):59–68. - PMC - PubMed
    1. Wisor JP, Schmidt MA, Clegern WC. Cerebral microglia mediate sleep/wake and neuroinflammatory effects of methamphetamine. Brain Behav Immun. 2011;25(4):767–76. - PubMed

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