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  • Title: Role of NMDA receptor activation in serotonin agonist-induced air-stepping in paraplegic mice.
    Author: Guertin PA.
    Journal: Spinal Cord; 2004 Mar; 42(3):185-90. PubMed ID: 14758350.
    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.
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