Subchronic administration of phencyclidine produces hypermethylation in the parvalbumin gene promoter in rat brain

Written by Fachim HA, Srisawat U, Dalton CF et al

The N-methyl-d-aspartate (NMDA) receptor antagonist phencyclidine (PCP) has been widely used in the investigation and modeling of psychotic illness. Subchronic administration of PCP to animals can induce brain metabolic and neurochemical changes [1] as well as behaviors [2] that mimic aspects of schizophrenia. Furthermore, this regime can also produce enduring deficits in several neurochemical markers that are also diminished in the brain in schizophrenia. These include the calcium binding protein parvalbumin (PV), which is expressed in a subgroup of GABAergic neurons and in schizophrenia demonstrates reductions in frontal cortical (PFC) regions [3] and, particularly profoundly, in the hippocampus [4]. Equivalent losses, typically greater than 50%, of PV-immunoreactive cells, are also seen in the rat hippocampus following subchronic PCP [2].
Deficits in immunostaining for PV-positive neurons have also been seen in other animal models that mimic some of the behavioral and also, in some models, the etiological characteristics of schizophrenia. These include isolation rearing [5], administration of neonatal endotoxin [6] and prenatal methylazoxymethanol [7] in rats, as well as following other psychotogenic drugs including ketamine [8,9] and amphetamine [10].

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