Administration of memantine reverses behavioral, histological, and electrophysiological abnormalities in rats subjected to early maternal deprivation.

ABSTRACT

Schizophrenia (SCZ) is a severe and chronic neurodevelopmental disorder with onset occurring during adolescence or early adulthood; notwithstanding, the brain dysfunction occurs before the disease and is not clinically evident. Recently, memantine (MEM) had been postulated as an effective preventive treatment in rats. In this study, was performed the Early Maternal Deprivation (EMD) protocol in Sprague-Dawley rats, establishing four groups (control, EMD, EMD treated with MEM, and MEM treatment). Behavioral parameters such as active linking (AL) and T maze were evaluated as well as quantitative brain histological changes at 3, 7, and 10 weeks of age, to understand the longitudinal demeanor of the disease. Prefrontal evoked potentials (PFEPs) were recorded to study functional synaptic connectivity and neuronal synchronicity changes. The results showed that EMD induces a decrease of AL and poor performance of T maze, in addition to volumetric changes of cortical and subcortical brain structures and abnormalities in PFEPs. The majority of this changes were absent by neonatal MEM administration. Taking into account that all these abnormalities are associated to SCZ, we propose to MEM as a potential preventive treatment.