Impact of chronic SSRI administration on memory parameters, lipid components and membrane properties in C57Bl/6J mice

Selective serotonin reuptake inhibitors (SSRIs) are well-documented for their impact on memory. Fluoxetine has both positive and negative effects on memory depending on the dose used, the length of administration, and the specific memory context. Conversely, escitalopram has been shown to enhance memory parameters. However, both compounds have the ability to modulate synaptic plasticity and neurogenesis. We selected compounds with these specific mechanisms of action to test our hypothesis.

We postulate that changes in memory parameters induced by SSRIs may result from changes in lipid composition, which affect the physicochemical properties of cell membranes and, consequently, the functional dynamics of memory.

Memory tests were conducted using modified Barnes maze (MBM) following chronic SSRI administration to evaluate our hypothesis. Subsequently, brain tissue samples were analyzed using Fourier Transform Infrared Spectroscopy (FT-IR) measurement for lipid changes detection, and atomic force microscopy to measure cell membranes' elastic modulus.

Chronic treatment with fluoxetine (10 mg/kg i.p.) possesses a negative impact on the general learning possibilities of mice and a positive impact on spatial learning in MBM. Influences wiping memory traces and working memory. Escitalopram (2 mg/kg i.p.) has a positive impact on memory parameters in MBM. Simultaneously, the prefrontal cortex (pFCx), hippocampus (Hc) and amygdala (Am) tissue revealed under the influence of chronic administration of SSRIs showed differences in lipid composition, which correspond with elastic modulus modifications.

Our findings indicate that chronic administration of SSRIs induces region-specific alterations in lipid composition and membrane elasticity, which parallel changes in memory performance. These results support the hypothesis that SSRI-related modulation of memory may be mediated, at least in part, by lipid-dependent regulation of neuronal membrane properties and synaptic plasticity.