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Depletion of platelet serotonin with a selective serotonin reuptake inhibitor does not improve survival in a mouse model of thromboembolism
Author(s) -
Liu Henry F,
Campbell Christina,
Hegde Sharath,
McNamara Alexander
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1116.3
Subject(s) - serotonin , platelet , paroxetine , serotonin reuptake inhibitor , serotonin transporter , fluoxetine , pharmacology , reuptake inhibitor , reuptake , medicine , platelet activation , chemistry , endocrinology , receptor
Platelet serotonin (5‐hydroxytryptamine, 5‐HT) is released upon platelet activation and serves as a proaggregatory factor. Clinical and preclinical evidence suggest that selective serotonin reuptake inhibitors (SSRIs) deplete platelet 5‐HT and reduce platelet aggregation. The goal of this study was to determine if inhibition of the 5‐HT transporter (SERT) reduces platelet 5‐HT and improves survival in a mouse thromboembolism (MTE) model. C57/BL6 mice were treated with vehicle (veh), fluoxetine (FX, 30 mg/kg, PO x 1 & 7d), paroxetine (PX, 30 mg/kg, PO x 7d), escitalopram (EC, 2 mg/kg, SC x 7d) or norfluoxetine (NFX, 5 mg/kg, IV x 1d). Mice were anesthetized and the right jugular vein cannulated. Thromboembolisms were induced with an infusion of collagen 200 μg/epinephrine 10 μg (Col/EPI), survival was monitored over the next 15 min and whole blood 5‐HT was measured. Col/EPI produced mortality in vehicle‐treated mice (~66 %). FX (7d) and NFX significantly enhanced survival (69 & 70 %), whereas FX (1d), PX and ES offered no survival benefit (≤ veh). SSRI treatment reduced whole blood 5‐HT by 75 – 99%; however, the decreased concentration of 5‐HT did not correlate with improved survival. Thus, depletion of platelet 5‐HT through SERT inhibition does not prevent Col/EPI induced‐thromboembolism in the MTE model. The efficacy of FX and NFX in this model appears to be independent of their SSRI activity. Source of Funding: None