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)

Previous reports suggesting that the behavioral response of the guinea pig to phencyclidine (PCP) administration is more similar to the effects of PCP observed in higher animals than those observed in mice and rats prompted us to investigate the effects of PC on spontaneous motor activity and brain biogenic amine levels in the guinea pig. Doses of 2.5 and 5.0 mg/kg PCP were found to significantly elevate spontaneous motor activity; however, 7.5 mg/kg PCP produced highly variable results which were not significantly different from control. The concentrations of tryptophan, serotonin, 5-hydroxyindoleacetic acid, and norepinephrine were measured in the forebrain and hindbrain of previously drug naive animals 30 min after administration of 5 mg/kg PCP. As compared to saline injected control animals, PCP was observed to have no effect on any of the neurochemical determinants measured. Contrary to previous reports, these data suggest that PCP produces behavioral effects in the guinea pig which are not unlike those observed in mice and rats. Furthermore, the effects which we report on spontaneous motor activity are not related to changes in the regional concentration of any of the neurochemical variables which were measured.
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PMID:Phencyclidine: effects on motor activity and brain biogenic amines in the guinea pig. 73 43

Phencyclidine (PCP; 20 micrograms in 0.5 microliter) was tested by local brain injection for neurochemical effects in the nucleus accumbens and striatum of rats. Changes in dopamine turnover could not be detected in postmortem tissue assays. In contrast, extracellular levels of dopamine significantly increased as measured by microdialysis in freely moving animals. PCP also increased extracellular levels of serotonin and decreased 3,4-dihydroxyphenylacetic acid (DOPAC), but did not change homovanillic acid (HVA) or 5-hydroxyindoleacetic acid (5HIAA). Microdialysis suggests that PCP acts in some dopamine terminal regions to increase extracellular dopamine and serotonin.
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PMID:Phencyclidine (PCP) injected in the nucleus accumbens increases extracellular dopamine and serotonin as measured by microdialysis. 245 34

The effects of phencyclidine (PCP) on the levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in discrete brain areas of mouse were investigated. Following a single administration, PCP significantly increased at 60 min the level of 5-HT but not 5-HIAA in the cortex. However, acute administration of PCP induced no changes of 5-HT and 5-HIAA levels in other brain areas investigated. On the other hand, chronic treatment of PCP produced a significant increase the striatal 5-HT and 5-HIAA levels by about 30% and 20%, respectively. These increased levels were gradually returned to the control levels, and there was no difference of these levels between the control group and the 48 hr withdrawal group. The changes of 5-HT level in the hypothalamus were similar to those in the striatum. These results suggest that the pharmacological actions of PCP and tolerance development to PCP may be related to the functional changes of serotonergic neuronal activity.
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PMID:Effects of acute and chronic administrations of phencyclidine on the levels of serotonin and 5-hydroxyindoleacetic acid in discrete brain areas of mouse. 257 8

Pregnant Sprague-Dawley rats were treated with 5 mg/kg body weight of phencyclidine (PCP) injected at 1 ml/kg subcutaneously on three consecutive days at four different stages of gestation. Within 10-30 min after treatment, dams showed some lack of motor coordination and became lethargic. On gestational day 21, all rats were killed by decapitation and brains were dissected and stored from mother and fetus for neurochemical analysis. PCP, dopamine and muscarinic cholinergic receptor binding was measured in membranes prepared from maternal and fetal whole brain. Neurotransmitter concentrations were also measured in the fetal brain homogenates. There was a significant decrease in PCP binding sites in fetal but not maternal brains after maternal PCP injection at gestational days 12-14, 15-17 and 18-20, but not at 9-11 days. Dopamine and muscarinic cholinergic receptor binding was not significantly altered in fetal or maternal brain when compared with vehicle control animals. The whole brain dopamine, 3,4-dihydroxyphenylacetic acid, serotonin, and 5-hydroxyindoleacetic acid concentrations did not show significant change in any group studied. These data indicate that gestational exposure to PCP decreases high affinity binding of PCP in term fetal brain at doses which do not alter maternal PCP receptor binding.
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PMID:Gestational exposure to phencyclidine (PCP) in rats decreases PCP binding sites in term fetal brain. 285 52

This study was designed to assess the involvement of serotonergic neurons in phencyclidine (PCP)-induced wet-dog shakes in rats after termination of reserpine treatment. Administration of L-5-hydroxytryptophan (7.5-12.5 mg/kg) to rats 30 min following pretreatment with pargyline induced wet-dog shakes which included head shake and whole body shake. p-Chloroamphetamine (PCA) (5 mg/kg) alone also produced wet-dog shakes in the vehicle-pretreated rats, but PCP (2.5-7.5 mg/kg) and tryptophan (100 mg/kg) alone did not. The number of wet-dog shakes significantly increased after the injection of PCA (2.5 and 5 mg/kg) in the reserpine-pretreated rats, in which the 5-hydroxyindoleacetic acid/serotonin (5-HT) ratio was significantly higher and postsynaptic 5-HT receptors were also in a state of supersensitivity, compared to that of the vehicle-pretreated rats. PCP (2.5-7.5 mg/kg) also produced wet-dog shakes in a dose-dependent fashion in rats after pretreatment with reserpine. Furthermore, PCP-induced wet-dog shakes were potentiated by imipramine, a 5-HT-uptake blocker, and prevented by mianserin, a 5-HT receptor-blocker. Tryptophan (100 mg/kg) alone produced wet-dog shakes in the reserpine-pretreated rats and it was enhanced in combination with imipramine. These results may indicate that the PCP-induced wet-dog shakes after reserpine withdrawal are due to an increased release of 5-HT from the functional pool and supersensitivity of postsynaptic 5-HT receptors.
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PMID:Phencyclidine-induced wet-dog shakes observed in rats after withdrawal from reserpine treatment. 372 29

The dose-dependent effects of systemically and locally administered phencyclidine (PCP) on the extracellular levels of dopamine, dihydroxyphenylacetate (DOPAC), homovanillate (HVA), 5-hydroxyindolacetate (5-HIAA), gamma-aminobutyrate (GABA), glutamate and aspartate in the dorsolateral striatum of anaesthetized rats were studied by in vivo microdialysis. Both local (1, 5, 50 and 100 microM) and systemic (2 and 10 mg kg-1 i.p.) PCP caused a dose-dependent increase in the extracellular levels of dopamine. The lowest PCP doses caused only a moderate but long-lasting increase in the extracellular levels of dopamine, while the highest PCP doses caused a massive but transient increase followed by a rebound decrease. The low doses of both systemic and local PCP tended to increase the levels of DOPAC, while those of HVA were not changed. The extracellular levels of 5-HIAA were increased only by the lowest (1 microM) locally administered dose of PCP. GABA levels were increased when PCP was administered locally at two doses. None of the treatments affected the extracellular levels of glutamate and aspartate. The results show that the effects of local and systemic PCP administration are dissimilar on the extracellular levels of 5-HIAA and GABA and thus provide new information on the neurochemical effects of PCP.
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PMID:In vivo effects of local and systemic phencyclidine on the extracellular levels of catecholamines and transmitter amino acids in the dorsolateral striatum of anaesthetized rats. 751 39

We have previously found that repeated phencyclidine (PCP) treatment enhances the immobility induced by forced swimming and suggested that this behavioral change could be used as a model of the negative symptoms, particularly depression, of schizophrenia. The present study attempted to examine the effects of antidepressants on the depressive states (immobility) induced by forced swimming in mice repeatedly treated with PCP, compared with those in mice repeatedly treated with saline. In mice repeatedly treated with saline, desipramine (5 and 10 mg/kg) and imipramine (5 and 10 mg/kg) significantly attenuated immobility, whereas mianserin (5-20 mg/kg) and clomipramine (10 and 50 mg/kg) had no affect. In mice repeatedly treated with PCP, the enhancing effect of PCP on immobility was attenuated by mianserin (5-20 mg/kg) at doses which did not have any effect in saline-treated mice, and by desipramine at higher doses (20 and 50 mg/kg). However, imipramine (5-20 mg/kg) and clomipramine (10-50 mg/kg) did not affect PCP-induced enhancement of immobility. In the biochemical study, the content of 5-hydroxyindoleacetic acid (5-HIAA) and the 5-HIAA/5-hydroxytryptamine (5-HT) ratio in the prefrontal cortex in mice repeatedly treated with PCP, but not with saline, following the forced swimming test were significantly increased, compared with those in the corresponding control mice (which did not perform the test). The present findings suggest that the depressive states induced by the forced swimming in mice repeatedly treated with PCP are less sensitive to acute treatment with tricyclic antidepressants, and this may be due to increase in 5-HT turnover. Antidepressants such as mianserin, which have the 5-HT2 receptor antagonist properties, may be useful for the treatment of negative symptoms of schizophrenia.
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PMID:Effects of antidepressants on phencyclidine-induced enhancement of immobility in a forced swimming test in mice. 914 63

Recent studies have indicated that the selective group II metabotropic glutamate (mGlu) receptor agonist (-)-2-oxa-4-aminobicyclo[3.1.0.]hexane-4,6-dicarboxylate (LY379268) shares common biochemical and pharmacological effects with the atypical antipsychotic clozapine. The present study aimed to further investigate these similarities (or differences) in monoamine-depleted animals by using the phencyclidine (PCP) model. Animals were pretreated 24 h before PCP administration with (i.p.) vehicle, alpha-methyl-DL-p-tyrosine methyl ester (alpha-MPT; 400 mg/kg), or DL-p-chlorophenyl-alanine methyl ester (PCPA; 300 mg/kg) injections. alpha-MPT and PCPA pretreatment significantly and selectively reduced catecholamine (dopamine and norepinepherine) or 5-hydroxytryptamine (5-HT, serotonin) and 5-hydroxyindoleacetic acid levels, respectively, in whole brain tissue. Both LY379268 and clozapine (s.c.) blocked PCP-evoked ambulatory activity and fine movements in control, alpha-MPT-, and PCPA-treated animals. In contrast, the typical antipsychotic haloperidol (s.c.) attenuated PCP behaviors in control and PCPA-pretreated animals, but was without effect in subjects pretreated with alpha-MPT. The alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid/kainate-selective antagonist (3S,4aR,6R,8aR)-6-[2-(1(2)OH-tetrazole-6-yl)ethyl]decahydroisoquinoline-3-carboxylic acid (LY293558) attenuated locomotor activity in alpha-MPT-treated animals only, whereas the 5-HT(2A/2C)-selective antagonist ketanserin was effective at reducing ambulations and fine movements in control and alpha-MPT-treated animals. Taken together, these data indicate an important role for glutamatergic and serotonergic mechanisms for PCP-evoked behaviors in catecholamine-depleted animals and suggest that like clozapine, LY379268 is more effective than typical antipsychotics in these models. This study further supports the potential use of group II mGlu agonists as novel therapeutic agents in the treatment of schizophrenia.
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PMID:The group II metabotropic glutamate receptor agonist (-)-2-oxa-4-aminobicyclo[3.1.0.]hexane-4,6-dicarboxylate (LY379268) and clozapine reverse phencyclidine-induced behaviors in monoamine-depleted rats. 1243 10

Several lines of research have implicated glutathione (GSH) in schizophrenia. For instance, GSH deficiency has been reported in the prefrontal cortex of schizophrenics in vivo. Further, in rats postnatal GSH-deficiency combined with hyperdopaminergia led to cognitive impairments in the adult. In the present report we studied the effects of 2-day GSH-deficiency with L-buthionine-(S,R)-sulfoximine on monoaminergic function in mice. The effect of GSH-deficiency per se and when combined with the amphetamine and phencyclidine (PCP) models of schizophrenia was investigated. GSH-deficiency significantly altered tissue levels of dopamine (DA), 5-hydroxytryptamine (5-HT) and their respective metabolites homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in a region-specific fashion. The effects of GSH-deficiency on tissue monoamines were distinct from and, generally, did not interact with the effects of amphetamine (5 mg/kg; i.p.) on tissue monoamines. Microdialysis studies showed that extracellular DA-release after amphetamine (5 mg/kg, i.p.) was two-fold increased in the nucleus accumbens of GSH-deficient mice as compared with control mice. Basal DA was unaltered. Further, extracellular levels of HVA in the frontal cortex and hippocampus and 5-HIAA in the nucleus accumbens were elevated by GSH-deficiency per se. Spontaneous locomotor activity in the open field was unchanged in GSH-deficient mice. In contrast, GSH-deficiency modulated the locomotor responses to mid-range doses of amphetamine (1.5 and 5 mg/kg, i.p.). Further, GSH-deficient mice displayed an increased locomotor response to low (2 and 3 mg/kg, i.p.) doses of phencyclidine (PCP). In conclusion, the data presented here show that even short-term GSH-deficiency has consequences for DA and 5-HT function. This was confirmed on both neurochemical and behavioral levels. How GSH and the monoamines interact needs further scrutiny. Moreover, the open field findings suggest reduced or altered N-methyl-d-aspartate (NMDA) receptor function in GSH-deficient mice. Thus, GSH-deficiency can lead to disturbances in DA, 5-HT and NMDA function, a finding that may have relevance for schizophrenia.
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PMID:Monoaminergic dysregulation in glutathione-deficient mice: possible relevance to schizophrenia? 1585 10