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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
Author(s) -
Cochran Susan M.,
Fujimura Masatake,
Morris Brian J.,
Pratt Judith A.
Publication year - 2002
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10126
Subject(s) - gabaergic , phencyclidine , neuroscience , glutamatergic , parvalbumin , ampa receptor , glutamate receptor , metabotropic glutamate receptor , medium spiny neuron , biology , endocrinology , nmda receptor , medicine , chemistry , dopamine , inhibitory postsynaptic potential , receptor , striatum
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 CaMKIIα, 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. Synapse 46:206–214, 2002. © 2002 Wiley‐Liss, Inc.