Ionotropic 5-HT<sub>3</sub> Receptor Agonist-Induced Motor Responses in the Hindlimbs of Paraplegic Mice
Bibliographic record
Abstract
Centrally expressed 5-HT3 receptors (5-HTR3) are well known for their role in wakefulness, cognition, and nociception. However, clear evidence of their participation in motor control is still lacking despite specific 5-HTR3 expression in hindlimb motor areas of the spinal cord (i.e., lumbar laminae VII-IX). Here, we studied the acute effects of 4-amino-(6-chloro-2-pyridyl)-1-piperidine hydrochloride (SR 57227A), a potent and selective 5-HTR3 agonist, on hindlimb movement generation in complete paraplegic mice. The induced movements were assessed in open-field, air-stepping, and treadmill conditions using a combination of qualitative and quantitative methods. The results revealed that SR 57227A (1-4 mg/kg ip) produced hindlimb movements corresponding to scores ranging from 1 to 5 on the motor scales of Basso, Beattie, and Bresnahan and of Antri, Orsal, and Barthe. Additional analyses revealed that one-third of the movements displayed on a treadmill were "locomotor-like" (i.e., bilateral alternation), whereas only nonlocomotor movements were observed in the other testing conditions suggesting a task-dependent contribution of peripheral afferent inputs to these effects. Locomotor-like movements could also be induced in open field and air stepping if SR 57227A was combined with subthreshold doses of 5-carboxytryptamine (5-HT1A/7 receptor agonist), suggesting synergistic actions of these drugs on central neurons. These results demonstrate that 5-HTR3 activation can induce motor activity and, under some conditions, rhythmic locomotor-like movements in the hindlimbs of paraplegic mice providing evidence of an unsuspected role for this receptor subtype in hindlimb motor control.
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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 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".