Serotonin refines the locomotor-related alternations in the in vitro neonatal rat spinal cord

Eur J Neurosci. 2005 Mar;21(5):1338-46. doi: 10.1111/j.1460-9568.2005.03971.x.


Serotonergic projections from raphe nuclei arrive in the lumbar enlargement of the spinal cord during the late fetal period in the rat, a time window during which the locomotor-related left/right and flexor/extensor coordinations switch from synchrony to alternation. The goal of the present study was to investigate the role played by serotonin (5-HT) in modulating the left/right and flexor/extensor alternations. Fictive locomotion was induced by bath application of N-methyl-D,L-aspartate (NMA) in the in vitro neonatal rat spinal cord preparation. By means of cross-correlation analysis we demonstrate that 5-HT, when added to NMA, improves left/right and flexor/extensor (recorded from the 3rd and 5th lumbar ventral roots, respectively) alternations. This effect was partly reproduced by activation of 5-HT(2A/2C) receptors. We then tested the contribution of endogenous 5-HT to NMA-induced fictive locomotion. Reducing the functional importance of endogenous 5-HT, either by inhibiting its synthesis with daily injections of p-chloro-phenylalanine (PCPA), starting on the day of birth, or by application of ketanserin (a 5-HT(2) receptor antagonist) or SB269970 (a 5-HT(7) receptor antagonist), disorganized the NMA-induced locomotor pattern. This pattern was restored in PCPA-treated animals by adding 5-HT to the bath. Blocking 5-HT(7) receptors disorganized the locomotor-like rhythm even in the absence of electrical activity in the brain stem, suggesting that NMA applied to the spinal cord does not cause 5-HT release by activating a spino-raphe-spinal loop. These results demonstrate that 5-HT is critical in improving the locomotor-related alternations in the neonatal rat.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Drug Interactions
  • Electrophysiology
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Fenclonine / pharmacology
  • Functional Laterality
  • In Vitro Techniques
  • Ketanserin / pharmacology
  • Motor Activity / drug effects
  • Motor Activity / physiology*
  • N-Methylaspartate / pharmacology
  • Phenols / pharmacology
  • Rats
  • Serotonin / physiology*
  • Serotonin Antagonists / pharmacology
  • Spinal Cord / drug effects
  • Spinal Cord / physiology*
  • Statistics as Topic
  • Sulfonamides / pharmacology


  • Drug Combinations
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Phenols
  • SB 269970
  • Serotonin Antagonists
  • Sulfonamides
  • Serotonin
  • N-Methylaspartate
  • Ketanserin
  • Fenclonine