Acute and delayed effects of phencyclidine upon mRNA levels of markers of glutamatergic and GABAergic neurotransmitter function in the rat brain

Authors

  • Susan M. Cochran,

    1. Yoshitomi Research Institute of Neuroscience in Glasgow (YRING), University of Glasgow, G12 8QQ, UK
    Search for more papers by this author
  • Masatake Fujimura,

    1. Pharmaceutical Research Division, Mitsubishi Pharma Corporation, Saitama, Japan
    Search for more papers by this author
  • Brian J. Morris,

    1. Yoshitomi Research Institute of Neuroscience in Glasgow (YRING), University of Glasgow, G12 8QQ, UK
    2. Institute of Biomedical and Life Sciences, University of Glasgow, G4 0NR, UK
    Search for more papers by this author
  • Judith A. Pratt

    Corresponding author
    1. Yoshitomi Research Institute of Neuroscience in Glasgow (YRING), University of Glasgow, G12 8QQ, UK
    2. Department of Physiology and Pharmacology, Strathclyde Institute for Biomedical Sciences, University of Strathclyde, Strathclyde Institute for Biomedical Sciences, Glasgow, G4 0NR, UK
    • Yoshitomi Research Institute of Neuroscience in Glasgow (YRING), West Medical Building, University of Glasgow, G12 8QQ, UK
    Search for more papers by this author

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 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.

Ancillary