AMPA receptors are involved in prefrontal direct current stimulation effects on long-term working memory and GAP-43 expression.

Anodal Direct Current Stimulation (DC) over prefrontal cortex improves working memory. This study investigated the influence of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) on prefrontal anodal DC-induced effects on spatial working memory and GAP-43 expression. Male Wistar rats well-trained in radial maze procedures received five sessions of anodal epidural DC stimulation (eDCS: 400 μA, 13 min, one daily session) over the left mPFC, or a respective sham procedure, and afterwards they received a single dose (1 mg/kg) of perampanel (PRP), an AMPARs antagonist, or vehicle 30 min before the performance of 4-h delayed task. The prefrontal cortex (PFC) and hippocampus (HPC) were removed 24-h later and GAP-43 (growth-associated protein) expression was measured by Western blot analysis. Repetitive eDCS decreased the number of errors in the 4-h post-delay performance (p < 0.05) and increased the expression of GAP-43 (p < 0.01) in the PFC when compared to sham stimulation. These behavioral and prefrontal molecular changes induced by the repetitive eDCS seem to involve AMPAR activity, because they were abolished when AMPARs were blocked by PRP (p < 0.01 and 0.05, respectively). Besides, in the HPC, changes of GAP-43 expression induced by eDCS was only seen when AMPARs were blocked by PRP. Therefore, the neuronal plasticity involving AMPARs may underlie, at least in part, the improving of spatial working memory and GAP-43 expression induced by the repetitive anodal prefrontal DC stimulation.