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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.

Abstract：

:Saturation and competition binding studies showed that the turtle brain contains sigma sites labeled by both [3H]di-o-tolylguanidine (DTG) and [3H](+)-pentazocine. There was a significant correlation between the IC50 values of sigma 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 sigma1 sites in the rodent brain, labels a heterogeneity of sites in the turtle brain. In extracellular recordings from the in vitro turtle brainstem, some sigma ligands enhanced the burst responses of red nucleus (RN) neurons (DTG, haloperidol, BD1031, BD1052, BD1069) while other sigma 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 sigma 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 sigma 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 sigma 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 sigma 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.

journal_name

Brain Res Bull

journal_title

Brain research bulletin

authors

Matsumoto RR,Bowen WD,de Costa BR,Houk JC

doi

10.1016/s0361-9230(99)00029-5

keywords:

subject

Has Abstract

pub_date

1999-03-15 00:00:00

pages

497-508

issue

eissn

0361-9230

issn

1873-2747

pii

S0361-9230(99)00029-5

journal_volume

pub_type

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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.