Neurodegeneration and prolonged immediate early gene expression throughout cortical areas of the rat brain following acute administration of dizocilpine.

摘要: Abstract N-methyl- d -aspartate receptor antagonist drugs (NMDA-A), such as dizocilpine (MK801), induce long-lasting behavioral disturbances reminiscent to psychotic disorders in humans. To identify cortical structures affected by NMDA-A, we used a single dose of MK801 (10 mg/kg) that caused low and high neurodegeneration intact orchiectomized male rats, respectively. Degenerating somas (neuronal death) axonal/synaptic endings (terminal degeneration) were depicted silver technique, functionally neuronal subpopulations Egr-1, c-Fos, FosB/ΔFosB-immunolabeling. In males, triggered c-Fos induction remained for more than 24 h selected layers the retrosplenial, somatosensory entorhinal cortices. MK801-induced reached its peak at 72 h. restricted layer IV granular subdivision retrosplenial cortex, accompanied suppression Egr-1 immunolabeling. Terminal degeneration extended parahippocampal cortices, which are target areas cortex. Induction FosB/ΔFosB also same terminal degeneration, likely reflecting damage synaptic connectivity. neurodegenerative functional effects exacerbated. Degenerative cortex significantly increased, with parallel enhancement FosB/ΔFosB-expression mentioned structures, but no additional affected. These observations reveal dysfunction/degeneration cortices might underlie impairments induced NMDA-A.