β-Funaltrexamine is protective against LPS-induced CXCL10 expression and behavioral impairments

Inflammation plays a pivotal role in neurological and peripheral disorders. Specifically, inflammation is one of the common factors in diseases such as anxiety, stress, depression, Alzheimer’s disease (AD), Parkinson’s disease (PD), and inflammatory bowel disease (IBD). Thus, exploring potential treatments geared toward the assessment of inflammation is crucial to the continuation of treatment development. One pharmacological agent researched for its anti-inflammatory effects is β-funaltrexamine (β-FNA), a selective mu-opioid receptor antagonist. Preclinical studies using in vitro human astroglial cells showed that β-FNA inhibited inflammatory signaling, NF-κB signaling, and chemokine expression in a mechanism unrelated to MOR. Also, β-funaltrexamines neuroprotective effects were discovered in a preclinical model of lipopolysaccharide (LPS)-induced neuroinflammation and sickness-like behavior when administered before LPS. This study determines the effects of β-FNA (50 mg/kg, i.p.) on LPS-induced (0.83 mg/kg, i.p.) sickness-like behavior using a 10 min open field test, and anxiety-like behavior, using a 5 min elevated plus maze in male and female C57BL/6J. It also assesses the effects on LPS-induced neuro and peripheral inflammation when β-FNA is administered immediately or 10 h post-LPS. Tissue collected included whole brain, hippocampus, prefrontal cortex, cerebellum/brain stem, spleen, liver, small intestine, large intestine, and plasma. Levels of inflammatory chemokine interferon gamma-induced protein 10 (IP-10, also known as CXCL10) was measured using an enzyme-linked immunosorbent assay (ELISA). Also, to our knowledge, this is the first time β-FNAs effect on female mice has been assessed. Differential effects of β-FNA were found between the whole brain vs. brain regions, central vs. peripheral, and sexes. This study provides insight into the inflammatory protection offered by β-FNA in both the central and peripheral systems and further knowledge of potential therapeutic options for neurological disorders.