Opiold- and Phencyclidine-Like Discriminative Effects of Ditolylguanidine, a Selective Sigma Ligand’

The sigma binding site in brain has affinity for psychotomimetic opiolds, phencyclidine (PCP) and antipsychotic drugs, and is a separate entity from the PCP receptor. In order to demonstrate a behavioral correlate of sigma binding, rats were trained to discriminate between s.c. injections of saline and 3.0 mg/kg of ditolylguanidine (DTG), a selective and high affinity sigma ligand, and tested for generalization to novel drugs. The rats generalized dose dependently and completely or almost completely to PCP and related drugs and to mu, kappa and sigma opioid agonists. A separate group of rats trained to discriminate saline from 2.0 mg/kg of PCP generalized completely to DTG, confirming the commonalities in the discriminative effects of these drugs. DTG-like discriminative effects of opioid enantiomers showed no con-sistent stereoselectivity. Discriminative effects of the DTG train