Dose-dependent effect of ketamine on functional connectivity in mice
Tomokazu Tsurugizawa, Aya Takemura
bioRxiv (Cold Spring Harbor Laboratory) September 8, 2026 preprint DOI: 10.64898/2026.09.03.749142 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study (animal experiment using fMRI) |
|---|---|
| Population | Mice |
| Intervention | Ketamine |
| Dose | 5 mg/kg and 50 mg/kg |
| Topics | Esketamine Ketamine |
| Key findings | Ketamine dose-dependently alters brain functional connectivity in awake mice: 5 mg/kg increases connectivity with thalamus and hypothalamus, while 50 mg/kg increases widespread connectivity with cortex, hippocampus, and thalamus, with hypothalamic and cortical regions central to network changes. |
Abstract
A single injection of a subanesthetic dose of ketamine, an NMDA receptor antagonist, induces schizophrenia-like behavior in mice. Previous studies investigated the effect of single injection of ketamine on behavior and c-Fos expression in mice dose-dependently. However, there has not been functional magnetic resonance imaging (fMRI) study to investigate the effect of ketamine in mice. Here, we used awake fMRI and investigated the dose-dependent effect of single injection of ketamine in awaked mice. The lower-dose (5 mg/kg) ketamine increased functional connectivity (FC) with the thalamus and the hypothalamic nuclei. Higher-dose (50 mg/kg) ketamine increased widespread FC with cerebral cortex as well as hippocampus and thalamic nuclei. Graph theory analysis reveals that several regions of hypothalamus and cerebral cortex are essential for the network change by ketamine injection. These results indicate that sub-anesthetic ketamine dose-dependently alters the brain and indues the abnormal behavior in mice.