Sevoflurane ameliorates schizophrenia in a mouse model and patients: pre-clinical and clinical feasibility study

Background: GABAergic deficits have been considered to associate with the pathophysiology of schizophrenia and hence GABA receptors subtype A (GABAARs) modulators such as commonly used volatile anesthetic sevoflurane, may have therapeutic values for schizophrenia. The present study investigates the therapeutic effectiveness of low-concentration sevoflurane in MK801-induced schizophrenia-like mice and schizophrenia patients.
Methods: Three weeks after MK801 administration (0.5 mg kg-1, i.p. twice a day, 5 days), mice were exposed to 1% sevoflurane 1hr/day for 5 days. Behavioral tests, immunohistochemical analysis, western blot assay and electrophysiology assessments were performed 1-week post-exposure. Ten schizophrenia patients received 1% sevoflurane for 5 hrs per day for 6 days and were assessed with Positive and Negative Syndrome Scale (PANSS) and the 18-item Brief Psychiatric Rating Scale (BPRS-18) at week 1 and week 2.
Results: MK801 induced hypolocomotion and social deficits, downregulated expression of NMDARs subunits and postsynaptic density protein 95 (PSD95), reduced parvalbumin - and GAD67-positive neurons, altered the amplitude and frequency of mEPSCs and mIPSCs and increased the excitation/inhibition ratio. All these changes induced by MK-801 were attenuated by sevoflurane administration. Six and eight patients achieved response defined as a reduction of at least 30% in the PANSS total score at 1st and 2nd week after treatments. The BPRS-18 total score was significantly decreased by 38% at 2nd week (p < 0.01).
Conclusion: Low-concentration sevoflurane effectively reversed MK801-induced schizophrenia-like disease in mice and alleviated schizophrenia patients’ symptoms. Our work suggested that sevoflurane may be a valuable therapeutic strategy for treating schizophrenia patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.