Contribution of spinal 5-HT1A and 5-HT7 receptors to locomotor-like movement induced by 8-OH-DPAT in spinal cord-transected mice.
Growing evidence from in vitro studies suggests that spinal serotonin (5-HT) receptor subtypes 5-HTR(1A) and 5-HTR(7) are associated with an induction of central pattern generator activity. However, the possibility of a specific role for these receptor subtypes in locomotor rhythmogenesis in vivo remains unclear. Here, we studied the effects of a single dose (1 mg/kg, i.p.) of 8-hydroxy-2-(di-N-propylamino)-tetralin (8-OH-DPAT), a potent and selective 5-HTR(1A/7) agonist, in mice spinal cord transected at the low-thoracic level (Th9/10). The results show that 8-OH-DPAT acutely induced, within 15 min, hindlimb movements that share some characteristics with normal locomotion. Paraplegic mice pretreated with the selective 5-HTR(1A) antagonists, WAY100,135 or WAY100,635, displayed significantly less 8-OH-DPAT-induced movement. A similar reduction of 8-OH-DPAT-induced movements was found in animals pretreated with SB269970, a selective 5-HTR(7) antagonist. Moreover, a near complete blockade of 8-OH-DPAT-induced movement was obtained in wild-type mice pretreated with 5-HTR(1A) and 5-HTR(7) antagonists, and in 5-HTR(7)-/- mice pretreated with 5-HTR(1A) antagonists. Overall, these results clearly demonstrate that 8-OH-DPAT potently induces locomotor-like movement in the previously paralysed hindlimbs of low-thoracic-transected mice. The results, with selective antagonists and knockout animals, provide compelling evidence of a specific contribution of both receptor subtypes to spinal locomotor rhythmogenesis in vivo.
Landry
Eric S
ES
Laval University Medical Center, Quebec, Canada.
Lapointe
Nicolas P
NP
Rouillard
Claude
C
Levesque
Daniel
D
Hedlund
Peter B
PB
Guertin
Pierre A
PA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004525:Efferent Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009416:Nerve Regeneration / Q000187:drug effects* / Q000235:genetics; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000235:genetics; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000235:genetics; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin