Iontophoretic effects of sigma ligands on rubral neurons in the rat.

Iontophoretic application of the sigma ligands, 1,3-di-o-tolylguanidine (DTG), dextrallorphan, and (+)-pentazocine reliably inhibited the firing rate of rubral neurons. Dextrallorphan inhibited 87% of the neurons tested, DTG inhibited 76%, and (+)-pentazocine inhibited 50%. These inhibitions were current dependent and occurred without significant changes in spike amplitude or duration, suggesting that local anesthetic effects were not involved. In contrast to the other sigma ligands, iontophoretic application of (+)-3-PPP in the rat red nucleus resulted in very few inhibitions and tended to elicit weak excitations instead. Only 14% of rubral neurons were inhibited by (+)-3PPP, while 36% were excited. Although unusual, (+)-3-PPP has atypical effects when compared to other sigma ligands in numerous functional assays for sigma receptor activity. (+)-3-PPP, therefore, appears to have complex effects and may act through nonsigma mechanisms or through a different type of sigma binding site than the other compounds. The inhibition of firing rate produced by the more typical sigma ligands may contribute to the postural changes produced by microinjection of sigma ligands into the rat red nucleus.