Repeated intermittent doses of phencyclidine (PCP) in rats caused deficits of N-acetylaspartate (NAA) and its precursor N-acetylaspartylglutamate (NAAG) specifically in the temporal cortex, while NAAG was elevated in the hippocampus. These changes mirror postmortem findings in schizophrenia, supporting the use of PCP-treated rats as a model for the neuronal dysfunction seen in that disease.
Chronic intermittent exposure to phencyclidine (PCP) in rats produces metabolic hypofunction in the prefrontal cortex, reticular nucleus of the thalamus, and auditory system—key brain regions that show similar changes in schizophrenia. PCP also decreases parvalbumin mRNA expression in the prefrontal cortex and reticular nucleus of the thalamus. Co-administration of the antipsychotics haloperidol or clozapine did not reverse PCP-induced metabolic reductions in the prefrontal cortex but did reverse deficits in auditory structures. Clozapine, but not haloperidol, reversed PCP-induced decreases in parvalbumin expression in prefrontal cortex GABAergic interneurons, while both drugs reversed deficits in the reticular nucleus of the thalamus. These findings strengthen the validity of chronic PCP as an animal model of schizophrenia and suggest that reversing prefrontal cortex parvalbumin deficits may be a marker of atypical antipsychotic activity.