In this study representatives from three chemical classes which are known to produce a phencyclidine (PCP)-like discriminative stimulus cue in rats were tested for their ability to inhibit synaptosomal uptake of 3H-dopamine (3H-DA) and to compete for a binding site labeled with 3H-PCP. Although there was a good correlation between these two in vitro activities within the arylcycloalkylamine class (PCP, N-ethyl-phenylcyclohexylamine (PCE), and ketamine) it did not hold when representatives from the benzomorphans, N-allynormetazocine (NANM), cyclazocine (CYCL), and ethylketocyclazocine (EKC), or a substituted dioxolane (etoxadrol) were included. At some dose each of these drugs with the exception of EKC also produced ipsilateral turning in rats with a unilateral 6-hydroxydopamine lesion of the substantia nigra. This effect was also not well correlated with inhibition of 3H-DA uptake. However, a significant correlation was found to exist between turning behavior and affinity for the putative PCP/sigma receptor. The possibility that a non-dopaminergic mechanism involving the PCP/sigma receptor underlies the ability of these agents to induce turning behavior is discussed.
Animals Benzomorphans