Acute ketamine administration modulates glutamatergic neurotransmission and functional brain activation in prefrontal cortex implications for major depression
Milan Scheidegger, A Henning, Martin Walter, Alexander Fuchs, Rainer Krähenmann, Heinz Böker, Peter Bösiger, Erich Seifritz, Simone Grimm
Pharmacopsychiatry September 1, 2011 DOI: 10.1055/s-0031-1292539 (opens in new tab) via OpenAlex
Summary
AI-generated from the abstractA subanaesthetic dose of ketamine alters brain activity during emotional processing and increases glutamate-glutamine cycling in the pregenual anterior cingulate cortex, a region linked to mood regulation. In 23 healthy subjects, ketamine infusion changed fMRI responses to emotional pictures, and these changes correlated with shifts in glutamine-to-glutamate ratios measured by spectroscopy. The findings suggest ketamine's rapid antidepressant effect may stem from enhanced glutamatergic neurotransmission.
Study at a glance
| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 23 |
| Population | Healthy subjects |
| Intervention | S-ketamine |
| Dose | 0.12 mg/kg i.v. bolus followed by 0.25 mg/kg/h over 60 min |
| Duration | 60-minute infusion |
| Topics | Ketamine |
| Keywords | Glutamatergic Glutamate receptor Nmda receptor Anterior cingulate cortex |
| Key finding | Changes in fMRI-BOLD responses during emotional processing correlated with glutamine to glutamate ratios in the pregenual anterior cingulate cortex after ketamine administration, suggesting increased glutamate-glutamine cycling. |
Abstract
Background: Ketamine is a potent NMDA receptor antagonist with rapid antidepressant properties at subanaesthetic doses. This multimodal imaging study reveals the effects of a subanaesthetic ketamine infusion on fMRI-BOLD responses during an emotional processing task and their relationship to glutamatergic metabolite concentrations in the pregenual anterior cingulate cortex (PACC) assessed by proton magnetic resonance spectroscopy (1H-MRS). Methods: 23 healthy subjects were asked to judge photographs from the International Affective Picture System (IAPS) by button press according to their valence in two separate fMRI sessions (baseline/ketamine) on a Philips 3T MR unit. S-ketamine was administered as an i.v. bolus of 0.12 mg/kg, followed by an infusion of 0.25 mg/kg/h over 60 min. 1H-MRS spectra from the bilateral PACC could be obtained in 16 subjects immediately after the task using a JPRESS sequence. Results and Conclusion: In the PACC, changes in NBRs correlated with glutamine to glutamate ratios as a putative marker of glutamatergic neurotransmission after ketamine administration compared to baseline. These changes are most likely interpreted in terms of an increased glutamate-glutamine-cycling rate after ketamine administration. Thus, the antidepressant effect of ketamine might be linked to a beneficial short-term influence on glutamatergic neurotransmission.