Effects of acute and chronic ketamine administration on spontaneous and evoked brain activity.

Acute suppression of NMDA receptors in mice alters brain oscillations across a wide frequency spectrum and diminishes oscillatory potency in evoked responses, paralleling changes seen in schizophrenia. Chronic suppression of NMDA receptors did not produce the expected cumulative effect on brain activity. The findings highlight robust yet similar impacts of acute and chronic NMDA receptor suppression on brain oscillations, contributing to a nuanced understanding of rodent models of schizophrenia.

Study at a glance

Abstract

Schizophrenia is believed to be, at least in part, a dysfunction of the glutamatergic system. In line with anatomical evidence, suppressing N-methyl-D-aspartate (NMDA) neurotransmission leads to symptoms that are characteristic of schizophrenia. Rodent models of schizophrenia often involve the acute application of NMDA antagonists, which produce both behavioural and brain activity changes that closely resemble symptoms observed in schizophrenia. It is, however, important to note that the full spectrum of schizophrenia symptoms may not be manifested following the acute suppression of NMDA receptors. This has led to the proposal of a chronic model where NMDA receptors are suppressed for prolonged periods. Although the chronic model has shown promising results from a behavioural perspective and alterations in metabolic processes in the brain, its impact on brain oscillations remains largely unknown. The aim of this study is to examine the impact of acute and chronic NMDA neurotransmission suppression on brains' oscillatory activity. To achieve this, chronic brain activity recordings in mice of both sexes were used to assess both spontaneous and evoked brain oscillations. The study demonstrates that an acute suppression of NMDA receptors alters brain oscillations across a wide frequency spectrum and diminishes the oscillatory potency in evoked responses, paralleling changes observed in schizophrenia. However, the chronic suppression of NMDA receptors did not have the expected cumulative effect on brain activity. This research highlights the robust yet similar impacts of acute and chronic NMDA receptor suppression on brain activity, contributing to the nuanced understanding of rodent models of schizophrenia.