520. INCREASE OF THE AMPA-EVOKED RESPONSE IN PREFRONTAL CORTEX PYRAMIDAL NEURONS FOLLOWING ACUTE ADMINISTRATION OF KETAMINE AND S-KETAMINE IN RATS
Bibliographic record
Abstract
Abstract Background Low dose ketamine has been shown, in animal studies, to enhance firing activity of norepinephrine neurons in the locus coeruleus, and burst as well as population activity of dopamine neurons in the ventral tegmental area [1]. These brainstem monoamine nuclei densely innervate the PFC, where clinical studies have shown a facilitation of glutamatergic neurotransmission in the PFC by a single injection of ketamine [2]. Aims & Objectives Due to reciprocal interactions between PFC glutamate neurons and monoamine neurons and their key role in the neurocircuitry of depression, the present electrophysiological study was aimed at investigating whether a single dose of ketamine has an effect on the AMPA- and NMDA-evoked responsiveness of PFC pyramidal neurons. Method Experiments were carried out on male Sprague Dawley rats weighing 275-300 g at the time of the experiments. Rats were anesthetized with chloral hydrate (400 mg/kg; ip) and mounted on a stereotaxic frame. Extracellular recordings of glutamate pyramidal neurons in the medial prefrontal cortex (mPFC) were carried out with five-barreled glass micropipettes. The central barrel used for the unitary recording was filled with a 2 M NaCl solution, and the impedance of these electrodes ranged from 2 to 4 MΩ. mPFC pyramidal neurons were identified using previously described criteria, and the responsiveness of these neurons to AMPA and NMDA applications by iontophoresis was assessed prior to and starting 30 minutes to 2 hours following administration of studied compounds. Results Despite mPFC pyramidal neurons displaying no change in their responsiveness to iontophoretically applied NMDA, an increase in responsiveness to iontophoretically applied AMPA was observed 30 minutes following ketamine and its enantiomer S-ketamine administration (10 mg/kg; two-Way repeated measures ANOVA, p < 0.001), when compared to saline treated rats. However, R-ketamine and the NMDA receptor GluN2B subunit antagonist ifenprodil have no effect on the responsiveness to AMPA and NMDA in mPFC pyramidal neurons compared to saline administered rats. Discussion & Conclusions Although both R-ketamine and ifenprodil were shown to have an antidepressant-like effect in the forced swim test [3,4], they do not seem to increase AMPA-induced response in the PFC, unlike racemic and S-ketamine. However, the increase in AMPA-induced response might constitute a common factor underlining the antidepressant-like effects of ketamine and S-ketamine. Such an increase coincides with an enhancement in expression of GluA1 subunit of AMPA receptors in the PFC in rat [5]. This is line with clinical studies showing that an increase in glucose metabolism, measured by 18F-FDG positron-emission tomography, suggesting an involvement of facilitation of glutamatergic neurotransmission in the PFC, which was correlated with the rapid antidepressant effect of low-dose of racemic ketamine [2].
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".