Depletion of platelet serotonin with a selective serotonin reuptake inhibitor does not improve survival in a mouse model of thromboembolism

• DOI: 10.1096/fasebj.26.1_supplement.1116.3
• Publication Date: 2021-06-21T15:15:00Z
• Authors: Henry F Liu; Christina Campbell; Sharath Hegde; Alexander McNamara
• Keywords: Paroxetine; Serotonin reuptake inhibitor; Reuptake

Platelet serotonin (5‐hydroxytryptamine, 5‐HT) is released upon platelet activation and serves as a proaggregatory factor. Clinical preclinical evidence suggest that selective reuptake inhibitors (SSRIs) deplete 5‐HT reduce aggregation. The goal of this study was to determine if inhibition the transporter (SERT) reduces improves survival in mouse thromboembolism (MTE) model. C57/BL6 mice were treated with vehicle (veh), fluoxetine (FX, 30 mg/kg, PO x 1 & 7d), paroxetine (PX, escitalopram (EC, 2 SC 7d) or norfluoxetine (NFX, 5 IV 1d). Mice anesthetized right jugular vein cannulated. Thromboembolisms induced an infusion collagen 200 μg/epinephrine 10 μg (Col/EPI), monitored over next 15 min whole blood measured. Col/EPI produced mortality vehicle‐treated (~66 %). FX (7d) NFX significantly enhanced (69 70 %), whereas (1d), PX ES offered no benefit (≤ veh). SSRI treatment reduced by 75 – 99%; however, decreased concentration did not correlate improved survival. Thus, depletion through SERT does prevent induced‐thromboembolism MTE efficacy model appears be independent their activity. Source Funding: None