266 Brain Research, 3861 IY,~O) 2t~ - 27~ BRE 12119 Phencyclidine (PCP) Receptors: Autoradiographic Localization in Brain with the Selective Ligand, [3H]TCP ANDREW L. GUNDLACH, BRIAN L. LARGENT and SOLOMON H. SNYDER Departments of Neuroscience, Pharmacology and Experimental Therapeutics, Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 (U.S.A. ) (Accepted 1 April 1986) Key words: Phencyclidine (PCP) -- [3H]TCP -- Quantitative autoradiography -- Receptor binding site -- Lesion -- Central nervous system -- Psychotomimetic Receptor binding sites for the phencyclidine (PCP) analogue, [3H]TCP, have been localized in the rat and guinea pig central ner- vous systems by in vitro autoradiography. Quantitation of [3H]TCP binding site densities in rat brain reveals highest levels in the fore- brain, in particular the strata oriens and radiatum of the hippocampus, the molecular layer of the dentate gyrus and superficial layers of the cerebral cortex. Moderate levels of binding occur in the amygdala, thalamus, anterior olfactory nucleus, external plexiform lay- er of the olfactory bulb, olfactory tubercle, geniculate nuclei and deep layers of the cortex. Low levels of binding occur throughout most of the septum, diagonal band, hypothalamus, pons-medulla and cerebellum. Spinal cord grey matter also has low levels of bind- ing. Excitotoxin lesions of the hippocampal formation, which destroy the pyramidal and granule cells, reduce the binding of [3H]TCP to strata radiatum and oriens and the molecular layer of the dentate gyrus by 60% suggesting that [3H]TCP labels intrinsic neurons in these regions. Residual binding is probably on afferent terminals. Ibotenic acid lesions of the caudate-putamen reduce [3H]TCP bind- ing by 70%, indicating that binding sites are localized on intrinsic striatal neurons. 6-Hydroxydopamine lesions do not alter [3H]TCP binding levels in the caudate, suggesting the absence of binding sites on dopaminergic terminals in the caudate. INTRODUCTION Phencyclidine (1-[1-phenylcyclohexyl]piperidine; PCP) is a widely abused psychoactive drug whose ef- fects resemble some primary symptoms of schizo- phrenia 5°. PCP interacts with many different neu- ronal systems. PCP and related drugs inhibit the reuptake and enhance the release of dopamine, nor- epinephrine and serotonin both in vitro 9A3'21'47'49 and in vivo 20'31'34 and alter the firing of monoamine neu- rons in vivo 12'29,40. PCP-like compounds antagonize the N-methyl-D-aspartate (NMDA)-induced excita- tion of spinal neurons in vivo 3'5'6 and cortical pyrami- dal cells in vitro 56 and block NMDA-induced acetyl- choline release from striatal slices 4s. Some of these effects may reflect interactions with potassium chan- n e l s ~,2.8. Receptor binding sites for [3H]PCP in brain ho- m o g e n a t e s 17,32,36,59,60,62 h a v e a p h a r m a c o l o g i c a l s p e c - ificity consistent with effects of PCP drugs in animal behavioral tests 11,43,63 as well as some physiological studies 6'7'3°'56 and might represent receptors for an endogenous PCP-like ligand 3s. Many studies have examined the putative association of PCP with opioids having psychotomimetic properties, i.e. cy opioids such as the benzomorphans, N-allylnormeta- zocine (SKF 10,047) and cyclazocine. Some radioli- gand binding and behavioral studies have suggested that PCP and a opioids mediate their unique behav- ioral effects through the same receptor si- te 33'43'44'46'61-63. Yet, more recent pharmacological and autoradiographic investigations suggest the PCP receptors are but one of two sites labeled by (+)- [3H]SKF 10,047, a o opioid, the other being a non- PCP a receptor binding site 16'26'27. Using (+)- [3H]SKF 10,047 as the radioligand, the high-affinity Correspondence: S.H. Snyder, Departments of Neuroscience, Pharmacology and Experimental Therapeutics, Psychiatry and Behav- ioral Sciences, The Johns Hopkins University School of Medicine, 750 North Wolfe Street, Baltimore, MD 21205, U.S.A. 0006-8993/86/$03.50 © 1986 Elsevier Science Publishers B .V. (Biomedical Division)