5-HT1A receptors are involved in short- and long-term processes responsible for 5-HT-induced locomotor function recovery in chronic spinal rat

Eur J Neurosci. 2003 Oct;18(7):1963-72. doi: 10.1046/j.1460-9568.2003.02916.x.

Abstract

After thoracic spinal cord transection, a paraplegic syndrome occurs. Previous data showed that an acute administration of a 5-HT2 agonist (quipazine) could promote motor function recovery in spinal rats. However, continuous subdural perfusion of quipazine via an osmotic pump over 1 month proved to be more effective. The present study was designed to investigate the possible involvement of 5-HT1A receptors in such recovery. Motor performances and locomotor parameters were analysed in spinal animals receiving daily, for 1 month, a dose of the 5-HT1A agonist 8-OHDPAT. The results were compared to those obtained in spinal rats receiving either a placebo or quipazine in the same conditions. Using daily injections instead of continuous perfusion of either receptor agonist to spinal animals allowed characterization of short- and long-term consequences of pharmacological stimulation of 5-HT1A and 5-HT2 receptors on motor function recovery. Our data demonstrate that daily injections of a 5-HT1A agonist induce long-term, cumulative, positive effects on motor function recovery, as assessed by the improvement in the walking parameters observed before the 'day-test' injection. This might involve use-dependent processes depending on a chronic and/or repetitive stimulation of the spinal network for locomotion in relation to 5-HT receptor activation. A further improvement in the motor parameters, transiently observed following the injection, suggests a more direct action of 5-HT1A and 5-HT2 receptor activation on spinal neurons involved in motor pattern generation.

Publication types

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

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Behavior, Animal
  • Biomechanical Phenomena
  • Electromyography / methods
  • Female
  • Hindlimb / physiopathology
  • Locomotion / drug effects*
  • Locomotion / physiology
  • Motor Activity / drug effects
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / physiopathology
  • Quipazine / pharmacology
  • Rats
  • Receptor, Serotonin, 5-HT1A / physiology*
  • Recovery of Function / drug effects*
  • Serotonin / pharmacology*
  • Serotonin Receptor Agonists / pharmacology
  • Spinal Cord Injuries / drug therapy
  • Spinal Cord Injuries / physiopathology*
  • Time Factors
  • Videotape Recording

Substances

  • Serotonin Receptor Agonists
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • Quipazine
  • 8-Hydroxy-2-(di-n-propylamino)tetralin