FLUOXETINE AND ESCITALOPRAM EXACERBATE EPILEPTIC ACTIVITIES AND INDUCE SOCIAL MEMORY DEFICITS IN THE TG2576 MOUSE MODEL OF ALZHEIMER’S DISEASE

Epileptic activities (EAs) are more prevalent in patients with Alzheimer’s disease (AD) than in the general population and have been associated with accelerated cognitive decline. In parallel, AD patients are at increased risk of depression, leading to the widespread use of antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs). However, these medications have been reported to increase EAs in the general population. We hypothesized that SSRIs may exacerbate EAs in AD and thereby accelerate cognitive decline. We tested this hypothesis in Tg2576 mice, a well-characterized Alzheimer’s disease model with a defined epileptic phenotype.
Tg2576 mice and non-transgenic littermates were chronically treated with Fluoxetine or Escitalopram via drinking water for 10 days. One group of mice underwent chronic ECoG recordings to quantify interictal spike (IIS) frequency and seizure occurrence, while another group was subjected to a social learning task.
As previously reported, Tg2576 mice exhibited spontaneous IIS at baseline. Fluoxetine treatment significantly increased IIS frequency by day five, and epileptic seizures emerged by day eight. This effect was partially prevented by p-chlorophenylalanine (pCPA). Chronic Escitalopram treatment also increased IIS frequency, but to a lesser extent than Fluoxetine, and did not induce epileptic seizures.
Both treatments specifically impaired social learning in Tg2576 mice compared with vehicle-treated Tg2576 mice and non-transgenic littermates.