Glial Glutamate Transporter Activator Prevents Inflammatory Pain and Major Depressive Disorder in a Mouse Model of Inflammation Induced by Lipopolysaccharide

Abstract ID 95168 Poster Board 123 Inflammatory pain and major depressive disorder (MDD) commonly co-exist affecting millions of people worldwide with significant socioeconomic impact. Emerging evidence suggests that increased inflammatory mediators can induce hyperactive glutamatergic neurotransmission involving glutamate transporter which contributes to comorbid pain and MDD. The objective of the present study was to determine the effects of glial glutamate transporter-1 (GLT-1) activator, LDN-212320, on pain, depression, and anxiety-like behaviors in a mouse model of inflammation for comorbid pain-MDD induced by lipopolysaccharide (LPS). Administration of LPS (1 mg/kg, i.p.) significantly decreased paw withdrawal threshold and latency time during von Frey and hot plate test to evaluate tactile allodynia and thermal hyperalgesia, respectively. Pretreatment with LDN-212320 (20 mg/kg, i.p.) increased paw withdrawal threshold in male mice but has little effect in female mice during von Frey test. Similarly, pretreatment with LDN-212320 (20 mg/kg, i.p.) increased latency time in both male and female mice during hot plate test. Administration of LPS (1 mg/kg, i.p.) significantly increased immobility time during forced swim test (FST) to measure depressive behavior and decreased open arm time in elevated plus maze (EPM) to measure anxiety-like behavior. Pretreatment with LDN-212320 (20 mg/kg, i.p.) decreased the immobility time and increased the open arm time in both male and female mice during FST and EPM test, respectively. Taken together, these results suggest that LDN-212320 reduces comorbid pain and depression-like behaviors in gender-specific manner likely by upregulating glial GLT-1 expression in the hippocampus and prefrontal cortex. Therefore, LDN-212320 could be a potential therapeutic candidate for further development as a novel treatment for comorbid pain and MDD.