Glycine site <i>N</i>-methyl-<scp>d</scp>-aspartate receptor antagonist 7-CTKA produces rapid antidepressant-like effects in male rats
Bibliographic record
Abstract
BACKGROUND: Glutamate N-methyl-D-aspartate (NMDA) receptor antagonists exert fast-acting antidepressant effects, providing a promising way to develop a new classification of antidepressant that targets the glutamatergic system. In the present study, we examined the potential antidepressant action of 7-chlorokynurenic acid (7-CTKA), a glycine recognition site NMDA receptor antagonist, in a series of behavioural models of depression and determined the molecular mechanisms that underlie the behavioural actions of 7-CTKA. METHODS: We administered the forced swim test, novelty-suppressed feeding test, learned helplessness paradigm and chronic mild stress (CMS) paradigm in male rats to evaluate the possible rapid antidepressant-like actions of 7-CTKA. In addition, we assessed phospho-glycogen synthase kinase-3β (p-GSK3β) level, mammalian target of rapamycin (mTOR) function, and postsynaptic protein expression in the medial prefrontal cortex (mPFC) and hippocampus. RESULTS: Acute 7-CTKA administration produced rapid antidepressant-like actions in several behavioural tests. It increased p-GSK3β, enhanced mTOR function and increased postsynaptic protein levels in the mPFC. Activation of GSK3β by LY294002 completely blocked the antidepressant-like effects of 7-CTKA. Moreover, 7-CTKA did not produce rewarding properties or abuse potential. LIMITATIONS: It is possible that 7-CTKA modulates glutamatergic transmission, thereby causing enduring alterations of GSK3β and mTOR signalling, although we did not provide direct evidence to support this possibility. Thus, the therapeutic involvement of synaptic adaptions engaged by 7-CTKA requires further study. CONCLUSION: Our findings demonstrate that acute 7-CTKA administration produced rapid antidepressant-like effects, indicating that the behavioural response to 7-CTKA is mediated by GSK3β and mTOR signalling function in the mPFC.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.002 |
| 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".