Candidate mechanisms underlying phencyclidine-induced psychosis: an electrophysiological behavioral, and biochemical study.
The central effects of phencyclidine (PCP) were investigated using electrophysiological, biochemical, and behavioral techniques. PCP produced depressions of neuronal firing of several brain regions when applied locally or parenterally. At the cerebellar locus coeruleus Purkinje neuron pathway PCP produced depressions of spontaneous firing. Use of lesion techniques and receptor antagonists revealed that at this synapse PCP acted as an agonist, i.e., an indirect sympathomimetic in that it caused release and or blocked reuptake of norepinephrine. PCP also produce alterations in behavioral measures such as stereotypy and rotarod performance. In addition PCP, like norepinephrine, produced increases in cyclic AMP levels in cerebellar slices. Inhibition of central neuron firing, and alterations in behavior were correlated with brain and blood levels of PCP. Many effects of PCP were antagonized by neuroleptics. It can be concluded that PCP has profound effects on several indices of central neuron function and such changes can be related to the psychosis and other effects of this drug.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D008125:Locus Coeruleus / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism; D010622:Phencyclidine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011605:Psychoses, Substance-Induced / Q000209:etiology*; D011689:Purkinje Cells / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*
D014150:Antipsychotic Agents; D011955:Receptors, Drug; D000242:Cyclic AMP; D010622:Phencyclidine; D009638:Norepinephrine