Propofol alleviates PTSD-like behavioral deficits by downregulating hippocampal Arc associated with GABAergic activation in basolateral amygdala in rats

Abstract Propofol (2,6-diisopropylphenol) is one of the most commonly used anesthetics in clinical surgery. However, its role and relevant mechanisms in post-traumatic stress disorder (PTSD)-like behavioral deficits remain largely unknown. In this study, the PTSD-like phenotype was constructed in rats using the modified single prolonged stress (MSPS) procedure. Propofol and GABAergic system antagonist bicuculline alone or combined administration were performed in rats after MSPS. SH-SY5Y cells were treated with different dosages of BDNF (1, 2, 5, 7 and 10 ng/ml), followed by treated with 25 µmol propofol. We first observed that propofol inhibited the protein level of activity regulated cytoskeleton protein (Arc) in the hippocampus of rats exposed to the MSPS procedure and BDNF-induced Arc upregulation in SH-SY5Y cells. Further analysis showed that administration of propofol alleviated fear memory formation in rats exposed to the MSPS procedure using open field, light dark box and contextual fear conditioning tests, accompanied with increased neurons cells in the hippocampal CA3 region by Nissl staining. Finally, administration of bicuculline to the basolateral amygdala (BLA) can significantly reverse the effect of propofol on the Arc expression and behavioral improvement of the modeling rats. In conclusions, our data suggested that propofol could alleviates fear memory formation in rats underwent MSPS by inhibiting Arc expression in the hippocampus in association with GABAergic activation in the basolateral amygdala GABAergic system.