Objective To investigate the impacts of maternal separation(MS)stress and the inhibition of the GABAA receptor alpha-6 subunit(Gabra6)on excitatory postsynaptic currents mediated by hippocampal AMPA receptors.Methods Newborn Sprague-Dawley rats were randomly divided into control and MS groups.The MS group underwent regular separation from their mothers to establish a rat model of maternal separation.Behavioral tests,including novelty-suppressed feeding,forced swimming,and sucrose preference were conducted to assess depressive behaviors in adolescent rats.Whole-cell patch-clamp recordings were used to measure evoked excitatory postsynaptic currents(eEPSCs)in the hippocampal CA1 region of control and MS rats.Results Adolescent MS rats exhibited prolonged latency to feed in a new environment(P<0.01)and increased immobility time in forced swimming(P<0.01).The Gabra6 antagonist furosemide significantly en-hanced eEPSCs recorded from pyramidal neurons in the CA1 region of the hippocampal slices(P<0.001).Chronic MS stress attenuated the enhancing effect of the Gabra6 antagonist furosemide on eEPSCs in the CA1 region of the hippocampal slices(P<0.05).Conclusion MS stress may alter the expression of hippocampal Gabra6,affecting excitatory postsynaptic currents,and induce depressive behaviors in rats,suggesting that drugs targeting GABA receptors may offer new strategies for depression treatment.