Relationship between modulation of the cerebellorubrospinal system in the in vitro turtle brain and changes in motor behavior in rats: Effects of novel sigma ligands

Rae R. Matsumoto*, Wayne D. Bowen, Brian R. De Costa, James C. Houk

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Saturation and competition binding studies showed that the turtle brain contains σ sites labeled by both [3H]di-o-tolylguanidine (DTG) and [3H](+)-pentazocine. There was a significant correlation between the IC50 values of σ ligands for [3H]DTG sites in the turtle vs. rat brain, suggesting that the sites are comparable in the two species. In contrast, [3H](+)-pentazocine, which primarily labels σ1 sites in the rodent brain, labels a heterogeneity of sites in the turtle brain. In extracellular recordings from the in vitro turtle brainstem, some σ ligands enhanced the burst responses of red nucleus (RN) neurons (DTG, haloperidol, BD1031, BD1052, BD1069) while other σ ligands decreased the burst responses (BD1047, BD1063). Control compounds (turtle Ringer vehicle control, opiate antagonist naloxone, atypical neuroleptic sulpiride) had no significant effects on the RN burst responses recorded from the in vitro turtle brain. The ED50s of the ligands for altering the burst responses in RN neurons from the turtle brain were correlated with their IC50s for turtle brain sites labeled with [3H]DTG, but not [3H](+)-pentazocine; this pattern is identical to that previously reported in rats, where there is a correlation between the potencies of σ ligands for producing dystonic postures after microinjection into the rat RN and their binding to rat brain sites labeled with [3H]DTG, but not [3H](+)-pentazocine. When the novel σ ligands were microinjected into the rat RN, dystonic postures were produced by ligands that increased the burst duration of RN neurons in the turtle brain. Novel σ ligands that reduced the burst responses in the in vitro turtle brain have previously been reported to have no effects on their own when microinjected into the rat RN, but to block the dystonic postures produced by other σ ligands. Taken together, the data suggest that the opposite effects of the novel ligands in the turtle electrophysiological studies represent the actions of agonists vs. antagonists, and that the directionality of the effects has predictive value for the expected motor effects of the drugs.

Original languageEnglish (US)
Pages (from-to)497-508
Number of pages12
JournalBrain Research Bulletin
Volume48
Issue number5
DOIs
StatePublished - Mar 15 1999

Keywords

  • Dystonia
  • Red nucleus
  • Sigma receptors
  • Turtle

ASJC Scopus subject areas

  • Neuroscience(all)

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