ANTINOCICEPTION FOLLOWING 1,3,-DI-O-TOLYLGUANIDINE, A SELECTIVE SIGMA-RECEPTOR LIGAND

The role of sigma receptors in antinociceptive processes remains equiv ocal, because previous sigma drugs also bind to PCP/NMDA and opiate re ceptors. The present study examined the antinociceptive effects of the high-affinity, sigma-selective ligand 1,3-di-o-tolylguanidine(DTG; 10 , 15, and 20 mg/kg, IP) on tail withdrawal latencies in mice. DTG prod uced significant but short-lived increases in withdrawal latencies at all dose levels. DTG also produced hypothermia, but this effect was di ssociable from antinociception. The highly selective sigma ligand rimc azole (10 and 25 mg/kg, IF) antagonized DTG antinociception in a dose- dependent manner. The opiate antagonist naloxone and the PCP/NMDA anta gonist MK-801 were, however, without effect. Haloperidol, which also b inds to sigma receptors, increased withdrawal latencies but did not al ter DTG antinociception. These data implicate sigma receptors as the s ite of DTG antinociception, and more generally support the distinction between sigma, opiate, and PCP/NMDA receptors.