Maternal separation stress induces depression in adolescent rats and weakens inhibitory effects of hippocampal Gabra6 on AMPA receptors
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.