Unusual Quadrupedal Locomotion in Rat during Recovery from Lumbar Spinal Blockade of 5-HT7 Receptors

Int J Mol Sci. 2021 Jun 2;22(11):6007. doi: 10.3390/ijms22116007.

Abstract

Coordination of four-limb movements during quadrupedal locomotion is controlled by supraspinal monoaminergic descending pathways, among which serotoninergic ones play a crucial role. Here we investigated the locomotor pattern during recovery from blockade of 5-HT7 or 5-HT2A receptors after intrathecal application of SB269970 or cyproheptadine in adult rats with chronic intrathecal cannula implanted in the lumbar spinal cord. The interlimb coordination was investigated based on electromyographic activity recorded from selected fore- and hindlimb muscles during rat locomotion on a treadmill. In the time of recovery after hindlimb transient paralysis, we noticed a presence of an unusual pattern of quadrupedal locomotion characterized by a doubling of forelimb stepping in relation to unaffected hindlimb stepping (2FL-1HL) after blockade of 5-HT7 receptors but not after blockade of 5-HT2A receptors. The 2FL-1HL pattern, although transient, was observed as a stable form of fore-hindlimb coupling during quadrupedal locomotion. We suggest that modulation of the 5-HT7 receptors on interneurons located in lamina VII with ascending projections to the forelimb spinal network can be responsible for the 2FL-1HL locomotor pattern. In support, our immunohistochemical analysis of the lumbar spinal cord demonstrated the presence of the 5-HT7 immunoreactive cells in the lamina VII, which were rarely 5-HT2A immunoreactive.

Keywords: 5-HT receptors; lumbar spinal cord; quadrupedal locomotion.

MeSH terms

  • Animals
  • Cyproheptadine / pharmacology
  • Electric Stimulation
  • Electromyography
  • Forelimb / drug effects
  • Forelimb / physiopathology
  • Hindlimb / drug effects
  • Hindlimb / physiopathology
  • Humans
  • Locomotion / drug effects
  • Locomotion / genetics*
  • Lumbosacral Region / physiopathology
  • Rats
  • Receptor, Serotonin, 5-HT2A / drug effects
  • Receptor, Serotonin, 5-HT2A / genetics*
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / genetics*
  • Serotonin / genetics
  • Serotonin / metabolism
  • Serotonin 5-HT2 Receptor Antagonists / pharmacology
  • Spinal Cord
  • Spinal Cord Injuries / drug therapy
  • Spinal Cord Injuries / genetics*
  • Spinal Cord Injuries / pathology
  • Spine / drug effects
  • Spine / physiopathology

Substances

  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin
  • Serotonin 5-HT2 Receptor Antagonists
  • serotonin 7 receptor
  • Cyproheptadine
  • Serotonin