Reproductive state matters when looking at the female brain and drug treatment effects

Studies with rats demonstrated the influence of pregnancy and SSRI administration on serotonin (5-HT) levels, synaptic density, and neurogenesis in the hippocampus.

Selective serotonin receptor inhibitors (SSRIs) can help alleviate mood and anxiety symptoms and are prescribed to 3.0% of pregnant women globally [1]. However, it is currently unknown if and how SSRIs affect the neurobiology of the brain in pregnant and postpartum women. Dr Jodi Pawluski (University of Rennes, France) discussed recent data on how a woman’s reproductive state (pregnant or postpartum) and SSRI use affect plasticity in the brain, especially in the hippocampus, a brain area integral in depression and SSRI efficacy [2].

In a rat model, the researchers showed that perinatal fluoxetine treatment reversed the effect of pre-gestational maternal stress on serum corticosterone levels and increased neurogenesis in the dorsal hippocampus [3]. Next, it was shown that pregnancy decreases the 5-HT turnover ratio (5-HIAA/5-HT) and increases synaptic density in the hippocampus (see Figure). In addition, short-term treatment with sertraline decreased 5-HT levels in the hippocampus dose-dependently in both pregnant and non-pregnant females and increased synaptic density only in non-pregnant females [4]. In contrast to the increase in synaptic density, a decrease of cell proliferation and neurogenesis was observed in the hippocampus of pregnant females [5].

Figure: Pregnancy and sertraline treatment decreased 5-HIAA/5-HT ratio in the hippocampus [4]

Reprinted from Pawluski JL, et al. Neuropharmacology. 2020;166:107950. Copyright 2020, with permission from Elsevier.

“So, reproductive state matters when looking at the female brain and drug treatment effects,” concluded Dr Pawluski. “Understanding the impact of reproductive state and SSRI medication on the maternal brain is essential to effectively treat, and ultimately prevent, perinatal mental illness.”

1. Molenaar NM, et al. J Affect Disord. 2020;264:82–89.
2. Pawluski JL, et al. SSRI effects on the hippocampus in pregnancy and postpartum – why reproductive state matters. Abstract S11.03, ECNP Congress 2022, 15–18 October, Vienna, Austria.
3. Gemmel M, et al. Behav Brain Res. 2018;339:222–223.
4. Pawluski JL, et al. Neuropharmacology. 2020;166:107950.
5. Pawluski JL, et al. Neurosci Biobehav Rev. 2022;133:104475.

 

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Posted on 28 November, 2022