Restoration of Excitation‐Inhibition Balance and Improvement of Schizophrenia‐like Behavioral Deficits via Electroacupuncture

BACKGROUND: Imbalances between excitatory and inhibitory signals have been implicated in the pathophysiology of schizophrenia. Electroacupuncture (EA) is commonly used in clinical practice to address neuropsychiatric conditions. However, the exact therapeutic mechanisms underlying EA's effects on schizophrenia remain poorly understood. METHODS: mice, which model the genetic deficits observed in schizophrenia, as a model system for our study. The locomotor activity, social behavior, sensorimotor gating ability, working memory, spatial learning and memory, and motor skills and coordination of mice were assessed using the open-field test, three-chamber social interaction test, prepulse inhibition (PPI) test, Y-maze, Morris water maze, and rotarod tests. Whole-cell patch-clamp recordings were performed to detect excitatory and inhibitory synaptic transmission and the intrinsic excitability of pyramidal neurons. RESULTS: EA alleviated behavioral deficits associated with schizophrenia in these mice. Notably, EA also enhanced GABAergic transmission and decreased the excitability of pyramidal neurons. Simultaneously, the selective nNOS inhibitor L-NPA blocked the therapeutic effects of EA on behavioral deficits and synaptic transmission. CONCLUSIONS: EA improved schizophrenia-like behavioral impairments and restored the balance between excitatory and inhibitory signaling, possibly through the upregulation of presynaptic GABA release. Furthermore, nitric oxide (NO) signaling may play a critical role in the observed benefits. These findings underscore the significance of excitatory-inhibitory (E/I) balance in mediating the therapeutic effects of EA, highlighting its potential as an intervention strategy for schizophrenia.