Effects of NMDA glutamatergic receptors pharmacological stimulation of the ventral tegmental area on the memory deficits induced by maternal deprivation

Abstract

Maternal deprivation (MD) is a potent stressor during early life and can lead to behavioral changes during adulthood. Several neurochemical mechanisms underlying MD-induced stress have been proposed; among them is the damage caused to dopaminergic neurons in the ventral tegmental area (VTA). We hypothesized that pharmacological stimulation of dopaminergic neurons in VTA by the infusion of an N-Methyl-D-Aspartate (NMDA) receptors agonist (used considering the wide distribution of these glutamatergic receptors in the VTA neurons) can reverse MD-induced memory deficits. Here, we demonstrated that MD affects male and female rats distinctly, with females being more resilient to early-life stress. Furthermore, NMDA pharmacological stimulation of the VTA promotes object recognition (OR) memory persistence in male and female non-MD rats. In males, infusion of NMDA into the VTA immediately after the learning session reverses recognition memory deficits related to MD. Although MD female rats have not shown deficits in OR memory consolidation, the NMDA infusion immediately after the learning session promotes memory persistence. We verified that MD leads to memory deficits in adult male rats, while the females are resilient to early life stress. Furthermore, NMDA pharmacological stimulation of dopaminergic VTA neurons reveals the dopaminergic modulation of OR memory in MD rats, even in females that did not exhibit memory deficits.

Keywords: Dopamine; Early life stress; Memory persistence; Object recognition memory; Ventral tegmental area.