Abstract
Cocaine abuse is known to cause inflammation, oxidative injury and alterations in the gut microbiota. Although emerging studies have demonstrated the role of gut microbiota in modulating neurological complications and behavior, the mechanism(s) underlying these processes remain unclear. In the present study, we investigated the protective effect of Lactobacillus rhamnosus probiotic on cocaine-induced oxidative stress, glial activation, and locomotion in mice. In this study, groups of male C56BL6 mice were administered gut-resident commensal bacteria L. rhamnosus probiotic (oral gavage) concurrently with cocaine (20 mg/kg, i.p.) or saline for 28 days and assessed for oxidative stress and cellular activation in both the gut and brain as well as alterations in locomotion behavior. Cocaine-induced gut dysregulation was associated with increased formation of 4-hydroxynonenal (4-HNE) adducts, increased expression of pERK-1/2, pNF-kB-p65 and antioxidant mediators (SOD1, GPx1). In cocaine administered mice, there was increased activation of both microglia and astrocytes in the striatum and cortex of the brain as shown by enhanced expression of CD11b and GFAP, respectively. Cocaine administration also resulted in increased locomotor activity in the open field test in these mice. Administration of L. rhamnosus attenuated cocaine-induced gut oxidative stress and inflammation as well as glial activation and locomotion. These results suggest the potential of microbial-based interventions to attenuate cocaine-mediated behavioral responses and neuroinflammation, in addition to systemic inflammation and oxidative damage.
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Acknowledgements
We are grateful to Dr. Mystera M Samuelson and the UNMC behavior Core Facility for assisting with the behavior assays and analysis. We are also grateful to Fang Niu for technical assistance.
Funding
This work was supported by NIH grant R01DA050545 (SB), R01DA050545-02S1 (PI: SB & ETC as Research Supplement recipient), R21DA046831 (ETC) and the Nebraska Centre for Substance Abuse Research (NCSAR).
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Experiments, data collection and analysis were performed by ETC, SS, SS, AT, LG, GBE, NF and SC. The first draft of the manuscript was written by ETC and all authors commented on previous versions of the manuscript. SB and ETC contributed to the study conception and design. All authors read and approved the final manuscript.
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Chivero, E.T., Sil, S., Singh, S. et al. Protective Role of Lactobacillus rhamnosus Probiotic in Reversing Cocaine-Induced Oxidative Stress, Glial Activation and Locomotion in Mice. J Neuroimmune Pharmacol 17, 62–75 (2022). https://doi.org/10.1007/s11481-021-10020-9
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DOI: https://doi.org/10.1007/s11481-021-10020-9