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* To whom correspondence should be addressed. E-mail: pierre.guertin{at}crchul.ulaval.ca.
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, i.p.) produced hindlimb movements corresponding to scores ranging from 1-5 on the motor scales of Basso, Beattie & Bresnahan and of Antri, Orsal & Barthe. Additional analyses revealed that one-third of the movements displayed on a treadmill were locomotor-like (i.e. bilateral alternation) whereas only non-locomotor 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 were 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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N. P. Lapointe and P. A. Guertin Synergistic Effects of D1/5 and 5-HT1A/7 Receptor Agonists on Locomotor Movement Induction in Complete Spinal Cord-Transected Mice J Neurophysiol, July 1, 2008; 100(1): 160 - 168. [Abstract] [Full Text] [PDF] |
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