Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Receptor binding sites for the phencyclidine (PCP) analogue, [3H]TCP, have been localized in the rat and guinea pig central nervous systems by in vitro autoradiography. Quantitation of [3H]TCP binding site densities in rat brain reveals highest levels in the forebrain, 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 layer 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 binding. 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 binding 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.
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PMID:Phencyclidine (PCP) receptors: autoradiographic localization in brain with the selective ligand, [3H]TCP. 302 81

Acute administration of phencyclidine to rats potently activates mesocorticolimbic dopaminergic neurons. The activation of dopamine release and utilization in the prefrontal cortex and nucleus accumbens are associated with profound cognitive impairment and hyperlocomotion, respectively. This dopaminergic activation by phencyclidine is not mediated by direct effects on the cell body regions of the dopamine neurons; however, phencyclidine augments dopamine release locally in the terminal fields. In the present study, the possible involvement of the prefrontal cortex in mediating activation of the mesolimbic dopamine system by phencyclidine was examined. Ibotenic acid lesions of the prefrontal cortex attenuated the biochemical activation of the mesolimbic dopamine neurons by PCP, and prefrontal lesions sharply blunted phencyclidine-, but not amphetamine- or novelty-, induced hyperlocomotion. In addition, injection of phencyclidine directly into the prefrontal cortex increased dopamine utilization in the nucleus accumbens and induced hyperlocomotion. In summary, these studies show that phencyclidine activates the mesolimbic pathway through a mechanism in the prefrontal cortex, possibly by disinhibiting the cortical circuit and activating corticofugal glutamatergic release in the ventral tegmental area.
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PMID:Prefrontal cortical involvement in phencyclidine-induced activation of the mesolimbic dopamine system: behavioral and neurochemical evidence. 969 31