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

Saturation and competition binding studies showed that the turtle brain con tains a sites labeled by both [H-3]di-o-tolylguanidine (DTG) and [H-3](+)-p entazocine. There was a significant correlation between the IC50 values of a ligands for [H-3]DTG sites in the turtle vs. rat brain, suggesting that t he sites are comparable in the two species. In contrast, [H-3](+)-pentazoci ne, which primarily labels al sites in the rodent brain, labels a heterogen eity of sites in the turtle brain. In extracellular recordings from the in vitro turtle brainstem, some a ligands enhanced the burst responses of red nucleus (RN) neurons (DTG, haloperidol, BD1031, BD1052, BD1069) while other a ligands decreased the burst responses (BD1047, BD1063). Control compound s (turtle Ringer vehicle control, opiate antagonist naloxone, atypical neur oleptic sulpiride) had no significant effects on the RN burst responses rec orded from the in vitro turtle brain. The ED(50)s of the ligands for alteri ng the burst responses in RN neurons from the turtle brain were correlated with their IC(50)s for turtle brain sites labeled with [H-3]DTG, but not [H -3](+)-pentazocine; this pattern is identical to that previously reported i n rats, where there is a correlation between the potencies of a ligands far producing dystonic postures after microinjection into the rat RN and their binding to rat brain sites labeled with [H-3]DTG, but not [H-3](+)-pentazo cine. When the novel a 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 a ligands that reduced the burst respons es in the in vitro turtle brain have previously been reported to have no ef fects on their own when microinjected into the rat RN, but to block the dys tonic postures produced by other a ligands. Taken together, the data sugges t that the opposite effects of the novel ligands in the turtle electrophysi ological studies represent the actions of agonists vs. antagonists, and tha t the directionality of the effects has predictive value for the expected m otor effects of the drugs. (C) 1999 Elsevier Science inc.