Ionotropic 5-HT3 receptor agonist-induced motor responses in the hindlimbs of paraplegic mice.
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 ip) produced hindlimb movements corresponding to scores ranging from 1 to 5 on the motor scales of Basso, Beattie, and Bresnahan and of Antri, Orsal, and Barthe. Additional analyses revealed that one-third of the movements displayed on a treadmill were "locomotor-like" (i.e., bilateral alternation), whereas only nonlocomotor 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 was 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.
Guertin
Pierre A
PA
Department of Anatomy and Physiology, Laval University and Laval University Medical Center, Quebec City, Quebec, Canada . pierre.guertin@crchul.ulaval.ca
Steuer
Inge
I
D000818:Animals; D001683:Biological Clocks / Q000187:drug effects*; D006614:Hindlimb / Q000187:drug effects / Q000503:physiopathology*; D007274:Injections, Intraperitoneal; D007473:Ion Channels; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology*; D010264:Paraplegia / Q000209:etiology / Q000503:physiopathology*; D010880:Piperidines / Q000008:administration & dosage*; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage; D013119:Spinal Cord Injuries / Q000150:complications / Q000503:physiopathology
D007473:Ion Channels; D010880:Piperidines; D044406:Receptors, Serotonin, 5-HT3; D017366:Serotonin Receptor Agonists; C083009:4-amino-1-(6-chloro-2-pyridyl)piperidine hydrochloride