title: Phencyclidine (PCP) and dizocilpine (MK801) exert time-dependent effects on the expression of immediate early genes in rat brain.
abstract: The mRNA expression pattern for four different immediate early genes was examined dynamically in rat brain after administration of phencyclidine (PCP; 0.86 or 8.6 mg/kg) or MK801 (0.1 or 1.0 mg/kg). Following each treatment, the expression of cfos, cjun, junB, and zif268 mRNA changed distinctively and dynamically between 1 and 48 hours. cfos mRNA was induced in cortical areas at early times after either dose of PCP or of MK801; the change was especially prominent in cingulate and auditory cortices. zif268 mRNA showed an early (1 hour) activation and a delayed (24-48 hour) suppression after PCP and MK801 in neocortical areas. PCP also caused cjun and junB mRNA induction in cortical areas at early times, with a distribution and time course similar to its effects on cfos mRNA. No alterations in cfos, cjun, or junB mRNA were found in neocortical or hippocampal areas at any delayed time (>6 hours) after PCP treatment, whereas suppression of zif268 expression was prominent even at 48 hours post-treatment. CPP, a competitive NMDA antagonist, showed a similar pattern of effects on cfos and zif268 mRNA expression. These functional consequences of a PCP- or MK801-induced reduction in NMDA-sensitive glutamate transmission may be relevant to an understanding of animal NMDA pharmacology and/or to clinical psychotomimetic side effects of antiglutamatergic treatments.
authors.affiliation: Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore 21228, USA.
authors.forename: X M
authors.initials: XM
authors.lastname: Gao
authors.forename: T
authors.initials: T
authors.lastname: Hashimoto
authors.forename: C A
authors.initials: CA
authors.lastname: Tamminga
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D017781:Genes, Immediate-Early / Q000187:drug effects*; D008297:Male; D010622:Phencyclidine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D018691:Excitatory Amino Acid Antagonists; D012333:RNA, Messenger; D016291:Dizocilpine Maleate; D010622:Phencyclidine