Behavioural therapy based on distraction alleviates impaired fear extinction in male serotonin transporter knockout rats
Bibliographic record
Abstract
BACKGROUND: The "biological susceptibility" model posits that some individuals, by genetic predisposition, are highly sensitive to environmental stimuli. Exposure to adverse stimuli leads to negative outcomes, and better outcomes follow favourable stimuli. Recent studies indicate that individuals carrying the low-activity (short; s) variant of the serotonin transporter (5-HTT)-linked polymorphic region (5-HTTLPR) show an enhanced vulnerability to posttraumatic stress disorder (PTSD). Simultaneously, they respond poorly to exposure therapy, the first-line treatment to enhance fear extinction in individuals with PTSD. Given that s-allele carriers also show improved adaptive responding when exposed to positive stimuli, we hypothesized that this trait could be used to offset impaired fear extinction. METHODS: We explored this hypothesis preclinically using wild-type and 5-HTT knockout (5-HTT-/-) male rats (n = 36) that share behavioural similarities with 5-HTTLPR s-allele carriers. Subsequent to cued fear conditioning, animals were tested for short- (1 and 2 days postconditioning) and long-term (6 days postconditioning) fear extinction in the absence or presence of a secondary "distracting" stimulus predicting the delivery of sucrose pellets. RESULTS: Introducing a secondary stimulus predicting sucrose pellets that distracts attention away from the fear-predicting stimulus led to a long-lasting improvement of impaired fear extinction in 5-HTT-/- male rats. LIMITATIONS: The contextdependency of the efficacy of the "distraction therapy" was not tested. In addition, it remains to be clarified whether the positive valence of the distracting stimulus is critical for the distraction of attention or whether a neutral and/or novel stimulus can induce similar effects. Finally, although of lesser importance from a therapeutic perspective, underlying mechanisms remain to be elucidated. CONCLUSION: These data indicate that positive environmental stimuli can be used to offset heightened responses to negative stimuli, particularly in individuals characterized by inherited 5-HTT downregulation and high sensitivity to environmental stimuli.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".