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 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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".