Sex-specific effects of subchronic NMDA receptor antagonist MK-801 treatment on hippocampal gamma oscillations.
Tim Simon Neuhäusel, Zoltan Gerevich
Frontiers in Neuroscience 2024 DOI: 10.3389/fnins.2024.1425323 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study in rats Peer reviewed |
|---|---|
| Population | Adult female and male rats |
| Intervention | MK-801 |
| Dose | 0.2 mg/kg daily |
| Duration | 14 days |
| Topics | Ketamine |
| Keywords | Cognition Electroencephalography EEG Electrophysiology Gamma oscillations Sex-specific Sex differences Brain waves Psychiatric drugs Mental health |
| Citations | 5 |
| Key findings | MK-801 treatment enhanced hippocampal gamma oscillations and altered behavior predominantly in female rats, indicating sex-specific effects of NMDA receptor blockade. |
Abstract
N-methyl-D-aspartate (NMDA) receptor antagonists are widely used to pharmacologically model schizophrenia and have been recently established in the treatment of treatment-resistant major depression demonstrating that the pharmacology of this substance class is complex. Cortical gamma oscillations, a rhythmic neuronal activity associated with cognitive processes, are increased in schizophrenia and deteriorated in depressive disorders and are increasingly used as biomarker in these neuropsychiatric diseases. The opposite use of NMDA receptor antagonists in schizophrenia and depression raises the question how their effects are in accordance with the observed disease pathophysiology and if these effects show a consequent sex-specificity. In this study in rats, we investigated the effects of subchronic (14 days) intraperitoneal injections of the NMDA receptor antagonist MK-801 at a subanesthetic daily dose of 0.2 mg/kg on the behavioral phenotype of adult female and male rats and on pharmacologically induced gamma oscillations measured ex vivo from the hippocampus. We found that MK-801 treatment leads to impaired recognition memory in the novel object recognition test, increased stereotypic behavior and reduced grooming, predominantly in female rats. MK-801 also increased the peak power of hippocampal gamma oscillations induced by kainate or acetylcholine only in female rats, without affecting the peak frequency of the oscillations. The findings indicate that blockade of NMDA receptors enhances gamma oscillations predominantly in female rats and this effect is associated with behavioral changes in females. The results are in accordance with clinical electrophysiological findings and highlight the importance of hippocampal gamma oscillations as a biomarker in schizophrenia and depression.
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 4
- The use of ketamine as an antidepressant: a systematic review and meta‐analysis Human Psychopharmacology: Clinical and Experimental April 7, 2015
- Ketamine in neuropsychiatric disorders: an update. Neuropsychopharmacology January 2024
- Increased inhibitory input to CA1 pyramidal cells alters hippocampal gamma frequency oscillations in the MK-801 model of acute psychosis. Neurobiology of Disease March 1, 2007
- Characterization of MK-801-induced behavior as a putative rat model of psychosis. Journal of Pharmacology and Experimental Therapeutics September 1, 1999