The neonatal ventral hippocampus (nVH) lesion in rats captures many features of schizophrenia at the levels of behavior and neurobiological markers. We have previously reported enhanced expression of α-1 adrenergic receptors (AR) in the prefrontal cortex (PFC) of postpubertal nVH-lesioned rats and proposed that enhanced α-1 AR signaling might participate in some of the behavioral abnormalities observed in the nVH-lesioned rats. To assess the components of α-1 adrenergic signaling in nVH-lesiond rats, we examined prefrontal cortical expression of protein kinase C (PKC) subtypes by Western blotting and α-1 AR-stimulated PKC activity by in vitro enzyme assay in postpubertal animals. Neonatal VH-lesioned animals showed significantly increased expression of membrane-bound PKC-α and the phosphorylated form of PKC. Cytosolic PKC-bII and PKC-γ expression were found to be decreased in the PFC of lesioned animals with no change in the expression of PKC-βI either in the cytosol or membrane. PKC activity assays showed an increase in basal PKC activity in the PFC slices of nVH-lesioned animals. Stimulation of α-1 adrenergic receptor with different concentrations of the agonist phenylephrine (PE), while increasing PKC activity in the sham-lesioned animals surprisingly decreased the activity in nVHlesioned animals. Increased basal levels as well as activity of prefrontal PKC and its anomalous regulation by α-1 adrenergic receptors may participate in the cognitive and stress-induced behavioral alterations in nVH-lesioned animals.
- Animal model
- Signal transudation