TRP canonical 4 and/or 5 channel inhibition reduces aversion‐ and increases reward‐responding in chronically stressed mice
Bibliographic record
Abstract
BACKGROUND AND PURPOSE: Pharmacological inhibition of TRPC4 and/or TRPC5 channels reduces Pavlovian aversion memory in stressed mice and reduces amygdala reactivity to aversion in humans with depression. The aims of this mouse study were to improve understanding of these anxiolytic processes, determine whether there are corrective effects on reward processes, and provide further translational evidence for TRPC4/C5 channel brain and neuron distribution. EXPERIMENTAL APPROACH: Mouse models of chronic social stress (CSS), with increased aversion and decreased reward responding, were applied to investigate the effects of a TRPC4/TRPC5 channel inhibitor. RT-qPCR and FISH were used to determine regional and neuronal gene expression. KEY RESULTS: Male mice underwent CSS, or were controls, and a TRPC4/TRPC5 inhibitor or vehicle was administered prior to Pavlovian aversion learning: stressed-vehicle mice displayed excessive Pavlovian learning, measured as high freezing to tone and context, and this was reduced by a TRPC4/TRPC5 inhibitor. Different stressed and control mice were tested on discriminative reward learning: there was no TRPC4/TRPC5 inhibitor effect on learning, but it did increase reward responding and effortful reward motivation in stressed mice. In naive male and female mice, Trpc4 and Trpc5 gene levels were moderate and high in glutamate principal neurons in basolateral amygdala and ventral hippocampus, respectively; co-expression with the CCKB receptor was substantial. TRPC4 and TRPC5 were expressed by glutamate neurons in human amygdala and hippocampus. CONCLUSIONS AND IMPLICATIONS: This study furthers understanding of the therapeutic potential of TRPC4/TRPC5 channel inhibition for excessive aversion processing and impaired reward processing.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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 source (direct Gemma or distilled Codex), 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".