Synergistic Effects of D<sub>1/5</sub> and 5-HT<sub>1A/7</sub> Receptor Agonists on Locomotor Movement Induction in Complete Spinal Cord–Transected Mice
Bibliographic record
Abstract
Monoamines are well known to modulate locomotion in several vertebrate species. Coapplication of dopamine (DA) and serotonin (5-HT) has also been shown to potently induce fictive locomotor rhythms in isolated spinal cord preparations. However, a synergistic contribution of these monoamines to locomotor rhythmogenesis in vivo has never been examined. Here, we characterized the effects induced by selective DA and 5-HT receptor agonists on hindlimb movement induction in completely spinal cord transected (adult) mice. Administration of the lowest effective doses of SKF-81297 (D 1/5 agonist, 1-2 mg/kg, ip) or 8-OH-DPAT (5-HT 1A/7 agonist, 0.5 mg/kg, ip) acutely elicited some locomotor-like movements (LM) (5.85 +/- 1.22 and 3.67 +/- 1.44 LM/min, respectively). Coadministration of the same doses of SKF-81297 and 8-OH-DPAT led to a significant increase (7- to 10-fold) of LM (37.70 +/- 5.01 LM/min). Weight-bearing and plantar foot placement capabilities were also found with the combination treatment only (i.e., with no assistance or other forms of stimulation). These results clearly show that D 1/5 and 5-HT 1A/7 receptor agonists can synergistically activate spinal locomotor networks and thus generate powerful basic stepping movements in complete paraplegic animals. Although previous work from this laboratory has reported the partial rhythmogenic potential of monoamines in vivo, the present study shows that drug combinations such as SKF-81297 and 8-OH-DPAT can elicit weight-bearing stepping.
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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) | 0.000 | 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".