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Acute and delayed effects of phencyclidine upon mRNA levels of markers of glutamatergic and GABAergic neurotransmitter function in the rat brain.
- Source :
-
Synapse (New York, N.Y.) [Synapse] 2002 Dec 01; Vol. 46 (3), pp. 206-14. - Publication Year :
- 2002
-
Abstract
- Glutamatergic and GABAergic neurotransmitter systems exist in equilibrium to maintain "normal" brain function. Evidence is accumulating that disturbance of this equilibrium may be one of the key factors giving rise to schizophrenia. While there is widespread evidence that the psychotomimetic phencyclidine (PCP) induces schizophrenia-related symptoms, it is not clear how this dramatic effect is mediated. This study was designed to investigate acute and delayed effects of PCP on the mRNA expression of a range of markers of neuronal function associated with the glutamatergic and GABAergic systems within the rat brain. The mRNA levels of CaMKIIalpha, an enzyme which is located within the postsynaptic density and phosphorylates AMPA receptors, remained unaltered both 2 and 24 h posttreatment. Homer 1a, an immediate early gene associated with metabotropic glutamate receptors within the postsynaptic density, displayed region-specific differential changes within the prefrontal, primary auditory, and retrosplenial cortices 2 and 24 h posttreatment. Parvalbumin, a calcium-binding protein located within a subpopulation of GABAergic interneurones, displayed altered mRNA levels within the reticular nucleus of the thalamus at 2 and 24 h posttreatment and the substantia nigra pars reticulata 24 h posttreatment only. These phencyclidine-induced changes in mRNA expression were not accompanied by any changes in hsp-70 mRNA levels, a marker of NMDA antagonist-induced reversible neurotoxicity. These results indicate that the glutamatergic (group I metabotropic glutamate receptors) and GABAergic (parvalbumin-containing interneurones) neurotransmitter systems are differentially modulated in a region- and time-dependent manner by exposure to phencyclidine.<br /> (Copyright 2002 Wiley-Liss, Inc.)
- Subjects :
- Animals
Brain metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases genetics
Carrier Proteins genetics
Carrier Proteins metabolism
Drug Administration Schedule
Excitatory Amino Acid Antagonists administration & dosage
Gene Expression drug effects
HSP70 Heat-Shock Proteins genetics
HSP70 Heat-Shock Proteins metabolism
Homer Scaffolding Proteins
In Situ Hybridization methods
Male
Neuropeptides genetics
Neuropeptides metabolism
Parvalbumins genetics
Parvalbumins metabolism
RNA, Messenger drug effects
RNA, Messenger metabolism
Rats
Rats, Long-Evans
Time Factors
Brain drug effects
Calcium-Calmodulin-Dependent Protein Kinases metabolism
Excitatory Amino Acid Antagonists pharmacology
Glutamic Acid physiology
Phencyclidine pharmacology
gamma-Aminobutyric Acid physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0887-4476
- Volume :
- 46
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Synapse (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 12325047
- Full Text :
- https://doi.org/10.1002/syn.10126