Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phencyclidine (PCP)-induced behavior in rats was investigated in water maze and diving behavior tasks. The swimming and diving latencies of PCP-treated groups placed in a water maze apparatus were gradually shortened, and prolonged, respectively, while rats in a control group performed well. In all rats, stereotyped behavior and hyperlocomotion were absent. We propose that this animal model induced by lower doses of PCP may be useful for further studies to research schizophrenia.
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PMID:A rat model of phencyclidine psychosis. 796 34

Phencyclidine (PCP; angel dust) is a drug of abuse known to produce a behavioral state in humans resembling schizophrenia/psychosis. PCP is a noncompetitive NMDA receptor antagonist and produces a variety of behaviors in rats including circling. The behavioral effects of other noncompetitive NMDA receptor antagonists such as (+)-MK-801 are still being elucidated. Here, adult female rats were dosed with PCP (10 mg/kg, IP), or (+)-MK-801 (0.1 mg/kg, IP) and circling preference was recorded for 2 h before sacrifice to determine monoamine levels by HPLC/EC. Animals injected with PCP or (+)-MK-801 showed a preference to turn to the left (65% and 72%, respectively). PCP and (+)-MK-801 also produced a significant increase of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in whole striatum on both sides of the brain. Further dissection of the striatum into medioventral and dorsolateral regions revealed that HVA was increased bilaterally except in globus pallidus where we found significant increases in dopamine (DA), DOPAC, and HVA only on the left side after PCP and (+)-MK-801 administration. These data suggest that PCP and (+)-MK-801 produce a greater preference to turn left than right, a finding similar to that found in human psychosis. Furthermore, it is possible that this preference to turn toward the left hemispace is due to an asymmetry in dopamine function found in the globus pallidus after administration of PCP and similar drugs.
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PMID:Phencyclidine and (+)-MK-801-induced circling preference: correlation with monoamine levels in striatum of the rat brain. 796 37

Phencyclidine induces a psychotomimetic state by blocking neurotransmission at N-methyl-D-aspartic acid (NMDA) receptors. In a double-blind, placebo-controlled fashion, 14 medicated patients with chronic schizophrenia were treated with glycine, a potentiator of NMDA-receptor-mediated neurotransmission. Significant improvement in negative symptoms occurred in the group given glycine but not in the group given placebo, suggesting that potentiation of NMDA-receptor-mediated neurotransmission may represent an effective treatment for neuroleptic-resistant negative symptoms in schizophrenia.
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PMID:Amelioration of negative symptoms in schizophrenia by glycine. 803 63

Phencyclidine (PCP)-induced psychosis is a useful animal model for studies on schizophrenia. N, N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)-phenyl]- ethylamine monohydrochloride (NE-100) had no effect on conditioned avoidance responses (CAR) in rats, whereas, the PCP-induced impairment of avoidance inhibition was attenuated by NE-100. The PCP-induced ataxia or decreased attention in rhesus monkeys was to some extent overcome by NE-100. In dogs, PCP-induced either head-weaving behavior or ataxia, effects which were blocked by NE-100. Administration of PCP led to an increase in beta-2 and a decrease in delta relative power (RP) activity in cortical background spectral electroencephalographics (ECoG) in dogs. While NE-100 in itself showed no significant change in beta-2 and delta RP, NE-100 did block the PCP-induced beta-2 increase and delta decrease. These findings indicate that NE-100 attenuates the effect of PCP in experimental animals. This drug is being considered as a therapeutic for the treatment of patients in the schizophrenia.
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PMID:NE-100, a novel sigma receptor ligand: effect on phencyclidine-induced behaviors in rats, dogs and monkeys. 804 Dec 25

Phencyclidine (PCP) produces schizophreniform psychoses in drug abusers and exacerbates symptoms in chronic schizophrenics. Although the exact mechanisms of psychotomimetic effects are unknown, the drug is known to act as an indirect dopamine (DA) agonist by inhibiting neuronal reuptake of DA. The drug is also known to work as a N-methyl-D-aspartate (NMDA) antagonist. Aiming to investigate characteristics of these two properties of PCP in the same experimental system, the effects of PCP on spontaneous and NMDA-induced DA efflux from superfused slices of rat striatum were examined. DA and 3,4-dihydroxyphenylacetic acid (DOPAC) in the superfusate samples were extracted via alumina extraction and measured by high-performance liquid chromatography with electrochemical detection (HPLC-ECD). PCP, at concentrations greater than 1 microM, produced a concentration-dependent increase of the spontaneous efflux of DA. DOPAC efflux was also concentration-dependently increased by PCP. However, PCP inhibited DA efflux induced by NMDA even at a low concentration (0.1 microM), which did not alter the spontaneous efflux of the transmitter. The mode of the inhibition of PCP was shown to be noncompetitive with an estimated IC 50 value of 280 nM. These results indicate that PCP acts simultaneously as a weak indirect DA agonist and as a potent noncompetitive NMDA antagonist. Since psychological change in normal subjects or exacerbation of schizophrenic symptoms has been reported to occur with a small dose of PCP, the psychotomimetic effects of the drug are more likely to be mediated by its interaction with NMDA receptor. The clinical significance of the present study is discussed in relation with the qlutamatergic hypothesis of schizophrenia.
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PMID:[A study on the pharmacological action of phencyclidine]. 809 62

Phencyclidine (PCP), a psychotomimetic drug of abuse, produces mental changes and manifestations in humans which are reminiscent of schizophrenia, though the mechanism of these actions remains unknown. We report here a biphasic time course of PCP action on regional cerebral glucose metabolism extending over 48 h. A single dose of PCP (8.6 mg/kg) produces an initial increase in glucose metabolism (at 3 h) and a later decrease in glucose metabolism (at 24 h) without a return to baseline until 48 h. A single lower dose of PCP (0.86 mg/kg), a dose which is considered selective for action at the NMDA-PCP receptor, produces no early metabolic change (at 3 h), but replicates the regional hypometabolism albeit less intense at 24 h. The delayed cerebral hypometabolism does not appear to be related to PCP-induced intracellular vacuolization, seen in the retrosplenial cortex. These metabolic changes may be associated with the psychotomimetic effects of PCP and thus may be relevant to psychosis in humans.
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PMID:Delayed regional metabolic actions of phencyclidine. 822 27

Glutamatergic hypothesis stemmed from the observation of phencyclidine-induced psychosis. Phencyclidine is able to induce in healthy subjects negative and positive schizophrenic-like symptoms, as well as thought disorganization. Phencyclidine acts as an antagonist of NMDA receptor, one of the glutamatergic receptors. Experimental studies in animals have demonstrated that compartmental effect of phencyclidine is due to its action at striatal level, allowing the disinhibition of down-stream structures. The organization of the two striato-thalamocortical loops, which exert, respectively, a positive and negative retro-control on cortical activity, may explain how a glutamatergic deficiency induces both positive and negative symptoms. Positive symptoms could also be due to a secondary hyperdopaminergia, since a part of striatum, the striosomes, connected with limbic system, control the activity of dopaminergic neurons. This model validates the hypothesis that a single anomaly can lead to the different symptomatic dimensions of schizophrenia and supports the implication of basal ganglia in the expression of mental disease.
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PMID:[Glutamatergic hypothesis of schizophrenia: psychoses induced by phencyclidine and cortical-subcortical imbalance]. 852 68

Current models of drug-induced psychosis insufficiently describe the symptoms of schizophrenia. Phencyclidine-induced psychosis is a model that more completely reflects the pathophysiology of the disease. By decreasing glutamatergic neurotransmission, phencyclidine decreases gamma-aminobutyric acid release from the nucleus accumbens, striatum, and hippocampus (manifested by MK-801); may inhibit tonic release of dopamine from the nucleus accumbens and striatum, resulting in increased dopamine phasic reactivity; and decreases long-term potentiation. Glutamatergic system dysfunction may be involved, but pharmacologic manipulation has not revealed a clear mechanism of this dysfunction.
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PMID:A review of NMDA receptors and the phencyclidine model of schizophrenia. 870 Jul 97

Phencyclidine (PCP) induces a psychotomimetic state that closely resembles schizophrenia, and PCP-treated animals can serve as a model for schizophrenia. The effects of PCP on the gene expression of NVP-1, a novel Ca(2+)-binding protein, were studied in rats. After 24 hours, the NVP-1 mRNA level in the nucleus accumbens showed a significant decrease of 42%. This result suggests that alterations in Ca(2+)-binding protein may be involved in the pathology of PCP-induced psychosis and, presumably, schizophrenia.
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PMID:Delayed changes in neural visinin-like calcium-binding protein gene expression caused by acute phencyclidine administration. 874 71

Phencyclidine (PCP) produces a psychotic reaction in humans which closely resembles an acute episode of schizophrenia and has therefore been given an increasing amount of attention as a model for schizophrenia. The present article reviews the behavioral and neurochemical effects of PCP in both humans and animals. Where possible, comparisons are made between the effects of PCP and amphetamine. The merits of the dopamine versus NMDA/PCP receptor mediated expression of PCP-induced psychosis are discussed, as well as the importance of selecting behavioral models which are best suited to model the expression of psychosis, rather than the motor effects of psychotomimetics.
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PMID:The behavioral and neurochemical effects of phencyclidine in humans and animals: some implications for modeling psychosis. 885 14


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