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

Received 4 February 2004; received in revised form 4 February 2004; accepted 4 February 2004.

Abstract

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 in the temporal cortex; NAAG was significantly elevated in the hippocampus. These changes closely reflect postmortem findings reported in schizophrenia.

Keywords: Schizophrenia, Phencyclidine (PCP), Rat, N-methyl-d-aspartate (NMDA) receptor, N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG)

a Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield S10 2TN, UK

b Yoshitomi Research Institute of Neuroscience in Glasgow, University of Glasgow, Glasgow G12 8QQ, UK

Corresponding author. Tel.: +44-114-222-2313; fax: +44-114-276-5413.

1 Current address of Gavin P. Reynolds, Department of Mental Health, Queen's University Belfast, Whitla Medical Building, 97 Lisburn Road, Belfast, BT9 7BL.

PII: S0920-9964(04)00051-9

doi:10.1016/j.schres.2004.02.003

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