Differential effects of 5-HT1 and 5-HT2 receptor agonists on hindlimb movements in paraplegic mice.
The effects induced by serotonergic (5-HT) agonists of the 5-HT1 and 5-HT2 subclasses were examined on hindlimb movement generation in adult mice completely spinal cord transected at the low thoracic level. One week postspinalization, intraperitoneal injection (0.5-10 mg/kg) of meta-chlorophenylpiperazine (m-CPP; 5-HT(2B/2C) agonist) or trifluoromethylpiperazine (TFMPP; 5-HT(1B) agonist) failed to induce locomotor-like movements. However, dose-dependent nonlocomotor movements were induced in air-stepping condition or on a motor-driven treadmill. In contrast, hindlimb locomotor-like movements were found after the injection of quipazine (5-HT(2A/2C) agonist; 1-2 mg/kg). Combined with L-DOPA (50 mg/kg, i.p.), low doses of quipazine but not of m-CPP and TFMPP produced locomotor-like and nonlocomotor movements in air-stepping condition or on the treadmill. Subsequent administration of m-CPP or TFMPP significantly reduced and often completely abolished the hindlimb movements induced by quipazine and L-DOPA. Altogether, these results demonstrate that 5-HT(2A/2C) receptor agonists promote locomotion while 5-HT(1B) and 5-HT(2B/2C) receptor agonists interfere with locomotor genesis in the hindlimbs of complete paraplegic mice. These results suggest that only subsets of spinal 5-HT receptors are specific to locomotor rhythmogenesis and should be activated to successfully induce stepping movements after spinal cord injury.
Landry
Eric S
ES
Department of Anatomy and Physiology, Laval University, Research Centre of the Laval University Research Hospital (CRCHUL-CHUQ), 2705 Bld Laurier, RC-9800, Quebec City, Quebec, G1V4G2, Canada.
Guertin
Pierre A
PA
D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004347:Drug Interactions; D005080:Exercise Test / Q000379:methods; D006614:Hindlimb / Q000187:drug effects* / Q000502:physiology; D007980:Levodopa / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D009068:Movement / Q000187:drug effects; D010264:Paraplegia / Q000503:physiopathology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011814:Quipazine / Q000494:pharmacology; D044263:Receptors, Serotonin, 5-HT1 / Q000378:metabolism; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy
D000978:Antiparkinson Agents; D010879:Piperazines; D011725:Pyridines; D044263:Receptors, Serotonin, 5-HT1; D044348:Receptors, Serotonin, 5-HT2; D058825:Serotonin 5-HT1 Receptor Agonists; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists; C407065:trifluoromethylpyridine; D007980:Levodopa; D011814:Quipazine; C015068:1-(3-chlorophenyl)piperazine