Differential effects of 5-HT1 and 5-HT2 receptor agonists on hindlimb movements in paraplegic mice

Prog Neuropsychopharmacol Biol Psychiatry. 2004 Sep;28(6):1053-60. doi: 10.1016/j.pnpbp.2004.05.001.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Antiparkinson Agents / pharmacology
  • Disease Models, Animal
  • Drug Interactions
  • Exercise Test / methods
  • Hindlimb / drug effects*
  • Hindlimb / physiology
  • Levodopa / pharmacology
  • Locomotion / drug effects
  • Male
  • Mice
  • Movement / drug effects
  • Paraplegia / physiopathology*
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Quipazine / pharmacology
  • Receptors, Serotonin, 5-HT1 / metabolism
  • Receptors, Serotonin, 5-HT2 / metabolism
  • Serotonin 5-HT1 Receptor Agonists*
  • Serotonin 5-HT2 Receptor Agonists*
  • Serotonin Receptor Agonists / pharmacology*
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / drug therapy

Substances

  • Antiparkinson Agents
  • Piperazines
  • Pyridines
  • Receptors, Serotonin, 5-HT1
  • Receptors, Serotonin, 5-HT2
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT2 Receptor Agonists
  • Serotonin Receptor Agonists
  • trifluoromethylpyridine
  • Levodopa
  • Quipazine
  • 1-(3-chlorophenyl)piperazine