Behavioral and morphological alterations following neonatal excitotoxic lesions of the medial prefrontal cortex in rats

Abstract

The prefrontal cortex (PFC) is essential for executive functions in mammals. Damage of the developing PFC may partly be compensated over time, but may also lead to structural and functional deficits due to neurodevelopmental disturbances. The present study investigated the effects of excitotoxic lesions of the medial PFC (mPFC) in neonatal rats on brain morphology, myelination and behavior. Neonatal lesions were induced with ibotenate on postnatal day (pd) 7 and all animals were tested pre- and postpubertally for prepulse inhibition (PPI) of the acoustic startle reflex (ASR), locomotor activity and food preference. Furthermore, adult rats were tested for apomorphine sensitivity of PPI and for their performance in a progressive ratio operant response task. Neonatally lesioned animals showed a reduced volume of the mPFC, enlarged ventricles and a deficient myelination in some projection areas of the mPFC, including the thalamus, hippocampus, nucleus accumbens (NAC) and amygdala. PPI was enhanced in lesioned rats when tested as juveniles, but PPI-deficits induced by the dopamine receptor agonist apomorphine were exacerbated in adult rats after neonatal mPFC lesion. Furthermore, the break point in a progressive ratio task was lower in lesioned animals, whereas the total number of lever presses was initially increased, indicating an impulsive response of rats for food reward under a progressive ratio schedule after neonatal mPFC lesion. No effects were found on food preference and open field performance. These data support the hypothesis that neonatal mPFC lesions lead to disruptions of neurodevelopmental processes in a cortico–limbic–striatal network, which are manifested in adult animals as morphological and behavioral disturbances.