Background: Major 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.
Methods: We 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.
Results: Individuals 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.
Conclusion: In 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.
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| http://dx.doi.org/10.1016/j.jpsychires.2022.06.016 | DOI Listing |
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