Dose-dependent effect of ketamine on functional connectivity in mice
- 1National Institute of Advanced Industrial Science and Technology (AIST)
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.
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BibTeX
@misc{tsurugizawa2026dosedependent,
title = {{Dose-dependent effect of ketamine on functional connectivity in mice}},
author = {T. Tsurugizawa and A. Takemura},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.03.749142},
url = {https://www.biorxiv.org/content/10.64898/2026.09.03.749142v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Dose-dependent effect of ketamine on functional connectivity in mice
AU - T. Tsurugizawa
AU - A. Takemura
PY - 2026
DA - 2026/09/03
PB - bioRxiv
DO - 10.64898/2026.09.03.749142
UR - https://www.biorxiv.org/content/10.64898/2026.09.03.749142v1
AB - 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.
ER -