Fluoxetine Treatment Decreases Cardiac Vagal Input and Alters the Serotonergic Modulation of the Parasympathetic Outflow in Diabetic Rats.

Mónica García-Domingo, José Ángel García-Pedraza, Juan Francisco Fernández-González, Cristina López, María Luisa Martín, Asunción Morán

International journal of molecular sciences 2022 May 20

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Comorbid diabetes and depression constitutes a major health problem, worsening associated cardiovascular diseases. Fluoxetine's (antidepressant) role on cardiac diabetic complications remains unknown. We determined whether fluoxetine modifies cardiac vagal input and its serotonergic modulation in male Wistar diabetic rats. Diabetes was induced by alloxan and maintained for 28 days. Fluoxetine was administered the last 14 days (10 mg/kg/day; p.o). Bradycardia was obtained by vagal stimulation (3, 6 and 9 Hz) or i.v. acetylcholine administrations (1, 5 and 10 μg/kg). Fluoxetine treatment diminished vagally-induced bradycardia. Administration of 5-HT originated a dual action on the bradycardia, augmenting it at low doses and diminishing it at high doses, reproduced by 5-CT (5-HT1/7 agonist). 5-CT did not alter the bradycardia induced by exogenous acetylcholine. Decrease of the vagally-induced bradycardia evoked by high doses of 5-HT and 5-CT was reproduced by L-694,247 (5-HT1D agonist) and blocked by prior administration of LY310762 (5-HT1D antagonist). Enhancement of the electrical-induced bradycardia by 5-CT (10 μg/kg) was abolished by pretreatment with SB269970 (5-HT7 receptor antagonist). Thus, oral fluoxetine treatment originates a decrease in cardiac cholinergic activity and changes 5-HT modulation of bradycardic responses in diabetes: prejunctional 5-HT7 receptors augment cholinergic-evoked bradycardic responses, whereas prejunctional 5-HT1D receptors inhibit vagally-induced bradycardia.

Citation

Mónica García-Domingo, José Ángel García-Pedraza, Juan Francisco Fernández-González, Cristina López, María Luisa Martín, Asunción Morán. Fluoxetine Treatment Decreases Cardiac Vagal Input and Alters the Serotonergic Modulation of the Parasympathetic Outflow in Diabetic Rats. International journal of molecular sciences. 2022 May 20;23(10)