The role of parvalbumin interneuron-mediated disinhibition in the antidepressant effects of ketamine / 医学研究生学报

ABSTRACT

ObjectiveTo observe the role of parvalbumin interneuron-mediated disinhibition in the antidepressant effects of ketamine.MethodsForty-eight adult male C57BL/6 mice were randomly divided into the following four groups (n=12) group Saline + Saline (group SS), group LPS + Saline (group LS), group Saline + Ketamine (group SK) and group LPS + Ketamine (group LK). The depression model was established by intraperitoneal injection of LPS (1 mg/kg), and ketamine (10 mg/kg) or physiological saline (equal volume) intraperitoneally injected 20 hours later. Four hours after ketamine administration, the open field test and the forced swimming test were performed. The hippocampus was harvested after the behavioral test. PCR and Western blot were used to detect the expressions of PV and GAD67. Electrophysiology were used to detect the change of miniExcitatory post-synaptic current of pyramidal neurons in hippocampus CA1 region.ResultsCompared with the group SS, the time spent in the center zone of the arena was significantly decreased, the immobility time was significantly increased, the mRNA and protein content of PV were significantly increased, the amplitude and frequency of miniEPSC were significantly decreased in the group LS (P0.05).ConclusionKetamine can exert rapid antidepressant effects by down-regulating the expression of PV and then exerting disinhibition regulation on pyramidal neurons.