Deficient adolescent social behavior following early-life inflammation is ameliorated by augmentation of anandamide signaling

摘要: Early-life inflammation has been shown to exert profound effects on brain development and behavior, including altered emotional stress responsivity neurochemical/neuropeptide receptor expression function. The current study extends this research by examining the impact of inflammation, triggered with bacterial compound lipopolysaccharide (LPS) postnatal day (P) 14, social behavior during adolescence. We investigated role that endocannabinoid (eCB) system plays in sociability after early-life LPS. To test this, multiple cohorts Sprague Dawley rats were injected LPS P14. In adolescence, subjected behavioral testing a reciprocal interaction paradigm as well open field. quantified eCB levels amygdala P14 adolescent animals (anandamide 2-arachidonoylglycerol) amygdaloid cannabinoid 1 (CB1) binding site density hydrolytic activity enzyme fatty acid amide hydrolase (FAAH), which metabolizes anandamide. Additionally, we examined FAAH inhibition alterations behavior. Our results indicate decreases (play non-play) males females at P40. This alteration is accompanied decreased CB1 binding, increased anandamide activity. Oral administration inhibitor PF-04457845 (1mg/kg) prior task normalizes LPS-induced while not affecting control group. Infusion 10ng into basolateral normalized females. These data suggest signaling following contribute impairments adolescence could be novel target for disorders involving deficits such anxiety or autism.