The involvement of the neuropeptides orexins (hypocretins) in fear and anxiety in rats exposed to a single episode of footshocks
Bibliographic record
Abstract
Post-traumatic stress disorder (PTSD) is a psychiatric condition that can develop when people experience a stressful and life-threatening event. Clinical research indicates that the presence of a state of hyperarousal after a traumatic experience is the best predictor of a subsequent diagnosis of PTSD. The role of arousal peptides called orexins (hypocretins) in a PTSD-like condition produced by exposing rats to a single episode of footshocks (5× 2 s episodes of 1.5 mA) was investigated in this thesis. The first part of my thesis involves the characterization of the footshock model of PTSD and the second part examines the involvement of orexins in this footshock model. The following findings are reported. First, shock rats that exhibited a high level of anxiety to a novel tone (high responders, HR) the day after the footshock exposure subsequently displayed more avoidance when compared to shock rats that exhibited a low level of anxiety (low responders, LR). These results highlight the importance of individual differences in the reaction to a strong fear-inducing experience. Second, the orexin precursor peptide prepro-orexin (ppOX) mRNA was found to be elevated in rats at 6 and 14 days after exposure to footshocks. In addition, ppOX mRNA levels were found to be positively correlated with anxiety at 14 days post-shock. Third, pre-shock injections of the corticotropin releasing factor receptor antagonist antalarmin were found to attenuate the anxiety expressed to the shock chamber and eliminate the correlation between ppOX mRNA levels and anxiety. Fourth, systemic injections of the nonselective orexin receptor antagonist TCS-1102 was found to attenuate the anxiety expressed in rats at 14 days post-shock. Fifth, TCS-1102 was found to have anxiolytic effects that were specific for the HR. The results of these experiments provide evidence linking the orexin system to the anxiety produced by exposure of rats to footshocks. They also provide preclinical evidence in support of the use of orexin antagonists for the treatment of anxiety in PTSD.
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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 | 0.000 | 0.000 |
| 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 | 0.000 | 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".