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

Sensory gating can be assessed using an auditory conditioning (C)-test (T) paradigm which measures the reduction in the auditory-evoked response produced by a test stimulus following a conditioning stimulus. Schizophrenic patients demonstrate absence of gating while dysfunction in glutamatergic neurotransmission is implicated in the pathophysiology of schizophrenia. This study examined the effect of the glutamate receptor antagonist, phencyclidine (PCP) on auditory gating in the CA3 region and dentate gyrus (DG) of rat hippocampus and medial prefrontal cortex (mPFC). Local field potential (LFP) activity was recorded simultaneously from CA3, DG and mPFC in isoflurane anaesthetised Lister hooded rats using in vivo electrophysiology. Paired auditory stimuli were presented binaurally over 128 trials. The effect of PCP (1 mg/kg, i.p.) on gating of the N2 LFP wave was assessed as the test:conditioning response amplitude ratio (T/C ratio); a value of < or =50% was indicative of gating. Auditory gating of the N2 wave was observed in the CA3, DG and mPFC. PCP disrupted gating in all three areas with significant increases in test amplitudes (P<0.001). Clozapine (5 mg/kg i.p) prevented the auditory gating deficits induced by PCP in the CA3, DG and mPFC. This study shows that PCP disrupts sensory gating in the CA3, DG and mPFC in the isoflurane anaesthetised rat. Similar deficits are observed in schizophrenic patients and the current method may provide an animal model with good predictive validity, a view substantiated by the fact that clozapine prevented the sensory gating deficits induced by PCP.
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PMID:Effects of phencyclidine on auditory gating in the rat hippocampus and the medial prefrontal cortex. 1969 83

Non-competitive antagonists of the N-methyl-d-aspartate receptor (NMDA) such as phencyclidine (PCP) elicit schizophrenia-like symptoms in healthy individuals. Similarly, PCP dosing in rats produces typical behavioral phenotypes that mimic human schizophrenia symptoms. Although schizophrenic behavioral phenotypes of the PCP model have been extensively studied, the underlying alterations of intrinsic neuronal properties and synaptic transmission in relevant limbic brain microcircuits remain elusive. Acute brain slice electrophysiology and immunostaining of inhibitory neurons were used to identify neuronal circuit alterations of the amygdala and hippocampus associated with changes in extinction of fear learning in rats following PCP treatment. Subchronic PCP application led to impaired long-term potentiation (LTP) and marked increases in the ratio of NMDA to 2-amino-3(5-methyl-3-oxo-1,2-oxazol-4-yl)propionic acid (AMPA) receptor-mediated currents at lateral amygdala (LA) principal neurons without alterations in parvalbumin (PV) as well as non-PV, glutamic acid decarboxylase 67 (GAD 67) immunopositive neurons. In addition, LTP was impaired at the Schaffer collateral to CA1 hippocampal pathway coincident with a reduction in colocalized PV and GAD67 immunopositive neurons in the CA3 hippocampal area. These effects occurred without changes in spontaneous events or intrinsic membrane properties of principal cells in the LA. The impairment of LTP at both amygdalar and hippocampal microcircuits, which play a key role in processing relevant survival information such as fear and extinction memory concurred with a disruption of extinction learning of fear conditioned responses. Our results show that subchronic PCP administration in rats impairs synaptic functioning in the amygdala and hippocampus as well as processing of fear-related memories.
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PMID:Synaptic transmission changes in fear memory circuits underlie key features of an animal model of schizophrenia. 2208 80

Animals exposed to phencyclidine (PCP) during the neonatal period have fewer GABAergic interneurons in the corticolimbic area, including the hippocampus, and exhibit abnormal behaviors after attaining maturation that correspond with schizophrenic symptoms. Since a lack of inhibitory interneurons in the hippocampus has also been reported in postmortem studies of patients with schizophrenia, the deficit may induce abnormal activity of hippocampal neurons that underlies pathological states in schizophrenia. However, it remains unclear how PCP treatment during the neonatal period affects the discharge activity of hippocampal neurons in adulthood. In the current study, single unit responses of hippocampal CA3 neurons to paired auditory clicks were recorded in freely moving mice repeatedly injected with PCP or saline during the neonatal period. The recorded neurons were classified into two subpopulations, narrow-spike neurons and broad-spike neurons, based on the spike width. The spontaneous discharge rate was higher in the narrow-spike neurons than in the broad-spike neurons, indicating that the narrow-spike neurons correspond with hippocampal inhibitory neurons. The proportion of narrow-spike neurons was significantly smaller in neonatally PCP-treated mice than in saline-treated mice. The broad-spike neurons that exhibited a response magnitude to the second click as large as that to the first click (E/E-type response) showed longer response duration to the paired clicks in PCP-treated mice than in the saline-treated mice. Further, the number of neurons with E/E-type response was higher in the PCP-treated mice than in the saline-treated mice. Finally, the attenuation of an auditory-evoked potential component, N40, to the second click (sensory gating) was blunted in the PCP-treated mice when compared with that in the saline-treated mice. These results suggest that the neonatal administration of PCP induced a deficit of inhibitory interneurons and altered discharge activity of neurons in the hippocampal CA3 region to the paired clicks, thereby inducing the deficit in sensory gating.
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PMID:Neonatal administration of phencyclidine decreases the number of putative inhibitory interneurons and increases neural excitability to auditory paired clicks in the hippocampal CA3 region of freely moving adult mice. 2290 77

Administration of N-methyl-D-aspartate receptor antagonist phencyclidine (PCP) to rat pups at postnatal day (PND) 7, 9, and 11 [neonatal PCP (neoPCP) model] induces cognitive deficits similar to those observed in schizophrenia. Expression of presynaptic SNARE protein, synaptosomal-associated protein of 25 kDa (Snap25), has been shown to be downregulated in postmortem brains from patients with schizophrenia. The present study was designed to investigate the long-term effects of neoPCP administration on expression of presynaptic markers altered in schizophrenia. Using radioactive in-situ hybridization, the expression of Snap25 was measured in the prefrontal cortex and the hippocampal formation (CA1, CA3, CA4, and dentate gyrus) at PND 29 and 80 in neoPCP and control rats. As a secondary presynaptic marker, the expressional level of synaptophysin was also measured in the same areas. Stereological estimation of the number of neurons and volume was used to exclude potential bias in cell numbers. A significant reduction in the expression of Snap25 in the hippocampal CA4 region was observed in adult neoPCP rats (PND 80, P<0.01), but not in preadolescent rats (PND 29), indicating a late developmental manifestation of a presynaptic pathology. The number of neurons and volume of the CA4 region showed no change in PCP rats compared with the controls. Furthermore, expression of another presynaptic marker, synaptophysin, remained unaffected by the PCP treatment. These findings indicate that perinatal PCP injections induce a delayed presynaptic impact on the vesicle fusion machinery in a brain region important for cognitive processes.
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PMID:Expression of presynaptic markers in a neurodevelopmental animal model with relevance to schizophrenia. 2404 78


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