Early environment contributes to developmental disruption of MPFC after neonatal ventral hippocampal lesions in rats.

Abstract

Using a putative animal model of schizophrenia, neonatal rat ventral hippocampal (VH) lesions, combined with cross-fostering Lewis and Fisher rats, we previously demonstrated that the postpubertal expression of amphetamine-induced hyperlocomotion after lesioning depends on the early environment of the pups. However, an important question that emerged from our studies was whether the early environment leads to sparing of function within the VH or to the disruption of another structure, such as the medial prefrontal cortex (MPFC). To answer this question, we took advantage of the natural variation in maternal care of Sprague-Dawley rat dams and separated them into high and low arched back nursing (ABN) groups. Then, on postnatal day 7 (PD7) the pups from the two groups of dams were lesioned in the VH. As a measure of VH function, the rats were tested in a reference memory paradigm, which demonstrated that nVH-lesioned rats raised by high or low ABN dams had pronounced deficits, suggesting that VH functions are not fully spared. Next, the integrity of the MPFC was tested in a number of paradigms in which MPFC function has been implicated. In all three paradigms a similar result was found, that only lesioned rats raised by high ABN dams displayed deficits, such as a lack of MPFC control of amphetamine-induced locomotion, decreased working memory, and decreased anxiety. These results suggest that the early environment does not affect the recovery of the VH to nVH lesion. Rather, the early environment interacts with nVH lesions in such a way that disrupts the development and function of MPFC.