No influence of mineralocorticoid and glutamatergic NMDA receptor stimulation on spatial learning and memory in individuals with major depression

Abstract

BackgroundMajor depressive disorder (MDD) is associated with impairments in spatial learning and memory and with altered functioning of central mineralocorticoid receptors (MR) and glutamatergic N-methyl-D-aspartate receptors (NMDA-R). Both receptors are highly expressed in the hippocampus and prefrontal cortex – brain areas that are critical for spatial learning and memory. Here, we examined the effects of separate and combined MR and NMDA-R stimulation on spatial learning and memory in individuals with MDD and healthy controls. MethodsWe used a randomized, double-blind, placebo-controlled between-group study design to examine the effects of separate and combined stimulation of the MR (with 0.4 mg fludrocortisone) and NMDA-R (with 250 mg D-cycloserine) in 116 unmedicated individuals with MDD (mean age: 34.7 ± 13.3 years; 78.4% women) and 116 age-, sex-, and education-matched healthy controls. Participants were randomly assigned to one of four conditions: 1) placebo; 2) MR stimulation; 3) NMDA-R stimulation; and 4) combined MR/NMDA-R stimulation. Three hours after drug administration, spatial learning and memory were assessed using a virtual Morris Water Maze task. ResultsIndividuals with MDD and healthy controls did not differ in spatial learning and memory performance. Neither separate nor combined MR or NMDA-R stimulation altered measures of spatial performance. ConclusionIn this study of relatively young, predominantly female, and unmedicated individuals, we found no effect of MDD and no effect of separate or combined MR and NMDA-R stimulation on spatial learning and memory.