In:
Current Neuropharmacology, Bentham Science Publishers Ltd., Vol. 20, No. 12 ( 2022-12), p. 2369-2380
Abstract:
GABAergic deficits have been considered to be associated 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 for 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 5 hrs per day for 6 days and were assessed with the 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 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 a 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 found to be significantly decreased by 38% at the 2nd week (p 〈 0.01). Conclusion: Low-concentration sevoflurane effectively reversed MK801-induced schizophrenialike
disease in mice and alleviated schizophrenia patients’ symptoms. Our work suggests sevoflurane to be a valuable therapeutic strategy for treating schizophrenia patients.
Type of Medium:
Online Resource
ISSN:
1570-159X
DOI:
10.2174/1570159X20666220310115846
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2022
detail.hit.zdb_id:
2119376-9
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