Effects of maternal depression and antidepressant treatment on neurotransmitters, brain regions, and mitochondrial function in rat dams

Increasing evidence suggests that mothers experience stress before or during pregnancy, which can significantly impact their GABAergic system and lead to amygdala hyperactivity. While animal models are expected to reflect the above findings in humans, the current knowledge on the effects of chronic unpredictable mild stress (CUMS) in rat dams remains insufficient. Therefore, the objective of this study was to investigate the structural and neurochemical alterations in the dorsal hippocampus, specifically gamma-aminobutyric acid (GABA) and glutamate (Glu) relative to total creatine (tCr), induced by the CUMS and the effects of antidepressant mirtazapine (MIR) treatment. Magnetic resonance imaging and proton localized magnetic resonance spectroscopy were used in rat dams at two time points to assess the reversibility of these alterations. Eight weeks post-CUMS, chronic stress induced significant alterations in hippocampal metabolism and structural changes, including lower GABA/tCr concentrations and an increased amygdala volume compared to controls. In stressed dams treated with MIR, no changes in GABA levels or amygdala volume were observed. Fourteen weeks post-CUMS, no significant changes in hippocampal neurochemistry were confirmed, while amygdala changes persisted in stressed dams. Moreover, significant time-dependent changes were observed in the amygdala and hypothalamus in the control group with MIR. Interestingly, high-resolution respirometry was performed to assess brain mitochondrial function, revealing only changes in this group. Based on these findings, we confirmed the reversibility of metabolite. Furthermore, MIR has demonstrated potential in regulating neurotransmitter levels and protecting amygdala volume after stress; however, further research is needed to fully understand its therapeutic effects.