Role of NMDA receptor activation in serotonin agonist-induced air-stepping in paraplegic mice.
METHODS
Experimental laboratory investigation of the effects of serotonergic and glutamatergic drugs in early paraplegic mice.


OBJECTIVE
To examine whether NMDA and 5-HT receptors synergistically participate to generate basic stepping movements in paraplegic mice.


METHODS
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.


CONCLUSIONS
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.
Guertin
P A
PA
Department of Anatomy and Physiology, Research Centre of the Laval University Medical center, Laval University, Quebec, Canada.
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D016202:N-Methylaspartate / Q000494:pharmacology; D010264:Paraplegia / Q000209:etiology / Q000503:physiopathology*; D011814:Quipazine / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000150:complications / Q000503:physiopathology; D013904:Thoracic Vertebrae
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D017366:Serotonin Receptor Agonists; D011814:Quipazine; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate