Mirtazapine modulates Glutamate and GABA levels in the animal model of maternal depression. MRI and 1H MRS study in female rats

Abstract

We aimed to determine, using in vivo magnetic resonance, whether maternal depression induced by chronic unpredictable stress (CUS) in the pre-gestational period in female rats would be evidenced by structural or neurometabolic changes in the hippocampal region of the brain. At the same time, appropriate behavioral tests were also administered after a relatively long two-month period of a stress paradigm. The objective of the study was not only to study an animal model of CUS using magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (¹H MRS) focused on the hippocampus, but also to use this technique to verify the effectiveness of mirtazapine antidepressant treatment. In the group with CUS, we found a significant decrease in the relative concentration of γ-aminobutyric acid (GABA/tCr) and glutamate+glutamine (Glx/tCr) compared to the control group, while we did not observe any statistically significant change in hippocampal volumes. Moreover, the forced swim test revealed an increase in depression-like behavior. The most important finding was the return of GABA/tCr and Glx/tCr levels to control levels during mirtazapine treatment; however, behavioral tests did not demonstrate any effects from mirtazapine treatment. In vivo¹H MRS confirmed mirtazapine modulation of CUS in an animal model more robustly than behavioral tests.

Keywords: (1)H MRS; Behavior; MRI; Maternal depression; Mirtazapine; Rat brain.