Acute Ketamine Infusion in Rat Does Not Affect In Vivo [11C]ABP688 Binding to Metabotropic Glutamate Receptor Subtype 5.
Lauren Kosten, Jeroen Verhaeghe, Leonie Wyffels, Sigrid Stroobants, Steven Staelens
Molecular imaging 2018 DOI: 10.1177/1536012118788636 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical imaging study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | Ketamine |
| Dose | subanesthetic doses |
| Measures | [11C]ABP688 PET binding |
| Topics | Ketamine Esketamine |
| Keywords | Glutamate Mglur5 Molecular imaging |
| Key points | Subanesthetic ketamine did not significantly change [11C]ABP688 binding to mGluR5 in any rat brain region, confirming prior rodent work with other NMDA receptor antagonists. The authors could not reproduce human findings of significant [11C]ABP688 binding decreases after ketamine bolus and infusion, and suggest species differences may account for the discrepancy. |
Abstract
Detecting changes in metabotropic glutamate receptor 5 (mGluR5) availability through molecular imaging with the positron emission tomography (PET) tracer [11C]ABP688 is valuable for studying dysfunctional glutamate transmission associated with neuropsychiatric disorders. Using an infusion protocol in rats, we visualized the acute effect of subanesthetic doses of ketamine on mGluR5 in rat brain. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist known to increase glutamate release. Imaging was performed with a high-affinity PET ligand [11C]ABP688, a negative allosteric modulator of mGluR5. Binding did not change significantly from baseline to ketamine in any region, thereby confirming previous literature with other NMDA receptor antagonists in rodents. Hence, in rats, we could not reproduce the findings in a human setup showing significant decreases in the [11C]ABP688 binding after a ketamine bolus followed by ketamine infusion. Species differences may have contributed to the different findings in the present study of rats. In conclusion, we could not confirm in rats that endogenous glutamate increases by ketamine infusion are reflected in [11C]ABP688 binding decreases as was previously shown for humans.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cites 3
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- Ketamine: 50 Years of Modulating the Mind Frontiers in Human Neuroscience November 29, 2016
- Ketamine-induced reduction in mGluR5 availability is associated with an antidepressant response: an [11C]ABP688 and PET imaging study in depression Molecular Psychiatry April 11, 2017