Effects of phencyclidine (PCP)-like drugs on turning behavior, 3H-dopamine uptake, and 3H-PCP binding.
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.
Johnson
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Snell
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D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology*; D001667:Binding, Competitive; D004148:Dioxolanes / Q000494:pharmacology*; D004149:Dioxoles / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D009019:Morphinans / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D017478:Receptors, Phencyclidine; D013574:Synaptosomes / Q000378:metabolism
D001575:Benzomorphans; D004148:Dioxolanes; D004149:Dioxoles; D009019:Morphinans; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D010622:Phencyclidine; D004298:Dopamine