Abstract:
STUDY DESIGN:Experimental laboratory investigation of the effects of serotonergic and glutamatergic drugs in early paraplegic mice. OBJECTIVES:To examine whether NMDA and 5-HT receptors synergistically participate to generate basic stepping movements in paraplegic mice. SETTING:Laval University Medical Center, Quebec, Canada. METHODS:Adult mice completely spinalized at the low-thoracic level 1 week earlier were suspended in harnesses for experiments. Acute drug-induced effects were examined on hindlimb movements filmed with a digital video camera. Detailed kinematic analyses included stick diagrams reconstructions of hindlimb movements and analysis of bilateral coordination, angular excursion, stepping amplitude and frequency. RESULTS:A single treatment with the 5-HT2 agonist quipazine (>0.7 mg/kg, i.p.) induced episodes of air-stepping movements in the hindlimbs of paraplegic mice. In contrast, injection of the glutamatergic agonist NMDA (1-45 mg/kg i.p.) failed to induce rhythmicity, although nonlocomotor rhythmic movements were observed with higher doses (45-60 mg/kg i.p.). Subthreshold doses of NMDA (22-30 mg/kg) could induce episodes of hindlimb air-stepping if combined with subthreshold doses of quipazine (0.3-0.7 mg/kg). Air-stepping was entirely blocked by administration of the selective NMDA antagonist MK-801. CONCLUSION:A single treatment with quipazine can trigger episodes of locomotor-like movements in early chronic spinal mice. Even though NMDA alone could not generate bilaterally coordinated air-stepping, NMDA receptor activation was nonetheless critical for spinal locomotor rhythmogenesis induced by 5-HT agonists in awake behaving animals.
journal_name
Spinal Cordjournal_title
Spinal cordauthors
Guertin PAdoi
10.1038/sj.sc.3101580subject
Has Abstractpub_date
2004-03-01 00:00:00pages
185-90issue
3eissn
1362-4393issn
1476-5624pii
3101580journal_volume
42pub_type
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