DISSOCIATION OF THE MOTOR EFFECTS OF (-PENTAZOCINE FROM BINDING TO SIGMA(1) SITES())

Radioligand binding and behavioral studies were conducted to determine whether a relationship existed between the motor effects produced by (+)-pentazocine and its binding to sigma sites. Scatchard analyses rev ealed decreased [H-3](+)-pentazocine binding in middle aged rats (5-6 months old) compared to young adult rats (2-3 months old). However, th ere was no difference between the extent of circling behavior or dysto nia produced by microinjection of (+)-pentazocine into the substantia nigra or red nucleus in the older animals compared to the young adult rats. There was also a significant decrease in [H-3](+)-pentazocine bi nding in rats chronically treated with haloperidol. Again, however, de spite the reduction in [H-3](+)-pentazocine binding, there was no diff erence between the extent of dystonia produced by unilateral intrarubr al microinjection of (+)-pentazocine into animals chronically treated with haloperidol vs. saline. The postural changes produced by (+)-pent azocine could not be attenuated with coadministration of the putative sigma receptor antagonist BD1047 enyl)ethyl]-N-methyl-2-(dimethylamino )ethylamine), or the opiate receptor antagonist naloxone. However, the (+)-opiate, (+)-nordihydrocodeinone, partially attenuated the postura l effects of(+)-pentazocine, despite its very low affinity for sigma(1 ), sigma(2) or opiate receptors. Taken together with previous studies, the results suggest that [H-3](+)-pentazocine is a potent and selecti ve probe for sigma(1) binding sites, but the in vivo effects of (+)-pe ntazocine cannot be fully attributed to actions through these sites. S ome of the in vivo effects of (+)-pentazocine appear to involve other binding sites that are not detected under the conditions normally used in in vitro assays.