Chronic phencyclidine administration induces schizophrenia-like changes in N-acetylaspartate and N-acetylaspartylglutamate in rat brain

@article{Reynolds2005ChronicPA,
  title={Chronic phencyclidine administration induces schizophrenia-like changes in N-acetylaspartate and N-acetylaspartylglutamate in rat brain},
  author={L. M. Reynolds and S. Cochran and B. Morris and J. Pratt and G. Reynolds},
  journal={Schizophrenia Research},
  year={2005},
  volume={73},
  pages={147-152}
}
Administration of phencyclidine (PCP) to both humans and animals models the symptoms of schizophrenia. Brain concentrations of N-acetylaspartate (NAA) are reduced in this disease, reflecting neuronal dysfunction. This study investigates the effects in rats of a chronic intermittent regime of PCP on NAA and its precursor N-acetylaspartylglutamate (NAAG) in rat frontal and temporal cortex, hippocampus and striatum, determined by HPLC. We found significant PCP-induced deficits of NAA and NAAG only… Expand
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References

SHOWING 1-10 OF 37 REFERENCES
The effect of treatment with antipsychotic drugs on brain N-acetylaspartate measures in patients with schizophrenia
TLDR
Results indicate that antipsychotic drugs increase N-acetylaspartate measures selectively in the dorsolateral prefrontal cortices of patients with schizophrenia, suggesting that these drugs modify in a regionally specific manner the function of a population of cortical neurons. Expand
Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs.
TLDR
These findings raise new questions regarding the safety of these agents in the clinical management of neurodegenerative diseases and reinforce concerns about the potential risks associated with illicit use of PCP. Expand
Distribution of N-acetylaspartylglutamate immunoreactivity in human brain and its alteration in neurodegenerative disease
TLDR
The results suggest that NAAG is substantially localized to putative glutamatergic pathways in human brain and that N AAG-LI neurons are vulnerable to the neurodegenerative process in HD and AD. Expand
N-acetylaspartate and N-Acetylaspartylglutamate deficits in superior temporal cortex in schizophrenia and bipolar disorder: a postmortem study
TLDR
The results are consistent with evidence of superior temporal cortex abnormalities in schizophrenia and the finding in bipolar disorder suggests that temporal cortex N-acetylaspartate deficits may be a common feature of psychotic disorders. Expand
Recent advances in the phencyclidine model of schizophrenia.
TLDR
It was found that PCP-induced psychotomimetic effects are associated with submicromolar serum concentrations of PCP and the findings suggest that endogenous dysfunction of NMDA receptor-mediated neurotransmission might contribute to the pathogenesis of schizophrenia. Expand
Induction of Metabolic Hypofunction and Neurochemical Deficits after Chronic Intermittent Exposure to Phencyclidine: Differential Modulation by Antipsychotic Drugs
TLDR
It is demonstrated that chronic intermittent exposure to PCP elicits a metabolic hypofunction, as demonstrated by reductions in the rates of glucose utilization, and proposed that reversal of PCP-induced reductions in parvalbumin expression in the prefrontal cortex may be a potential marker of atypical antipsychotic activity in relation to amelioration of cognitive deficits and negative symptoms of schizophrenia. Expand
The Neuropsychopharmacology of Phencyclidine: From NMDA Receptor Hypofunction to the Dopamine Hypothesis of Schizophrenia
TLDR
To support the contention that NMDA receptor antagonist administration represents a viable model of schizophrenia, the behavioral and neurobiological effects of these drugs are discussed, especially with regard to differing profiles following single-dose and long-term exposure. Expand
N-acetylaspartylglutamate, N-acetylaspartate, and N-acetylated alpha-linked acidic dipeptidase in human brain and their alterations in Huntington and Alzheimer's diseases.
TLDR
It is shown that the decreases in the levels of NAAG and NAA and in the activity of NAALADase in AD and HD brain correlate primarily with neuronal loss, and that there is a close relationship between N AAG and the dipeptidase NAALadase in populations of affected neurons. Expand
Glutamate receptor dysfunction and schizophrenia.
TLDR
It is proposed that since N-methyl-D-aspartate receptor hypofunction can cause psychosis in humans and corticolimbic neurodegenerative changes in the rat brain, and since these changes are prevented by certain antipsychotic drugs, including atypical neuroleptic agents, a better understanding of this mechanism may lead to improved pharmacotherapy in schizophrenia. Expand
Abnormal excitatory neurotransmitter metabolism in schizophrenic brains.
TLDR
The hypothesis that schizophrenia results from a hypofunction of certain glutamatergic neuronal systems is supported and the therapeutic efficacy of neuroleptics may be related to increased glutamatorgic activity. Expand
...
1
2
3
4
...