Central 5‐<scp>HT</scp><sub>1A</sub> receptor‐mediated modulation of heart rate dynamics and its adjustment by conditioned and unconditioned fear in mice
Bibliographic record
Abstract
BACKGROUND AND PURPOSE: The beat-by-beat fluctuation (dynamics) of heart rate (HR) depends on centrally mediated control of the autonomic nervous system (ANS) reflecting the physiological state of an organism. 5-HT1A receptors are implicated in affective disorders,associated with ANS dysregulation which increases cardiac risk but their role in autonomic HR regulation under physiological conditions is insufficiently characterized. EXPERIMENTAL APPROACH: The effects of subcutaneously administered 5-HT1A receptor ligands on HR dynamics were investigated in C57BL/6 mice during stress-free conditions and emotional challenge (recall of fear conditioned to an auditory stimulus and novelty exposure) using time domain and non-linear HR analyses. KEY RESULTS: Pre-training treatment with of 8-OH-DPAT (0.5 mg·kg(-1) , s.c.) prevented conditioned tachycardia in the retention test indicating impaired fear memory. Pretest 5-HT1A receptor activation by 8-OH-DPAT (0.5 but not 0.1 and 0.02 mg·kg(-1) ) caused bradycardia and increased HR variability. 8-OH-DPAT (0.5 mg·kg(-1) ) lowered the unconditioned and conditioned tachycardia from ∼750 to ∼550 bpm, without changing the conditioned HR response to the sound. 8-OH-DPAT induced profound QT prolongation and bradyarrhythmic episodes. Non-linear analysis indicated a pathological state of HR dynamics after 8-OH-DPAT (0.5 mg·kg(-1) ) with ANS hyperactivation impairing HR adaptability. The 5-HT1A receptor antagonist WAY-100635 (0.03 mg·kg(-1) ) blocked these effects of 8-OH-DPAT. CONCLUSIONS AND IMPLICATIONS: Pre-training 5-HT1A receptor activation by 8-OH-DPAT (0.5 mg·kg(-1) ) impaired memory of conditioned auditory fear based on an attenuated HR increase, whereas pretest administration did not prevent the fear-conditioned HR increase but induced pathological HR dynamics through central ANS dysregulation with cardiac effects similar to acute SSRI overdose.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".