α-Chloralose diminishes γ oscillations in rat hippocampal slices

α-Chloralose is an anesthetic characterized by its ability to maintain animals in physiological conditions though immobilized and anesthetized. In addition, α-chloralose induces a loss of consciousness with little influence on either pain response or cardiovascular reflexes. The pharmacological mechanisms of α-chloralose's actions are poorly understood. In vitro experiments have demonstrated α-chloralose enhances GABAA receptor function, which may underlie its anesthetic effect. However, how α-chloralose affects hippocampal synaptic function and neuronal network synchronization is unknown. In the present study, we performed electrophysiological recordings to examine the effects of α-chloralose on synaptic transmission, tetanic stimulation-induced γ oscillations (30–80 Hz) and neuronal receptor function in rat hippocampal slices and dissociated hippocampal CA1 pyramidal neurons. The results demonstrated that α-chloralose (30–100 μM) diminished tetanic stimulation-induced γ oscillations without affecting single stimulation-induced field potential responses. In single, dissociated hippocampal CA1 pyramidal neurons, α-chloralose activated GABAA receptors at a high concentration while it potentiated GABAA receptor-mediated currents at low concentrations. However, α-chloralose did not affect glutamate-, glycine-, or ACh-induced currents. Slice-patch recordings revealed α-chloralose enhanced GABAergic leak current and prolonged the decay constant of spontaneous inhibitory postsynaptic currents (sIPSCs). It is concluded that α-chloralose suppresses hippocampal γ oscillations without significantly affecting basic synaptic transmission or ionotropic glutamate, choline and glycine receptor function. Enhancement of GABAergic leak current and prolongation of GABAergic sIPSCs by α-chloralose likely underlie its disruption of neuronal network synchronization in the hippocampus.