{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T18:06:45Z","timestamp":1778350005644,"version":"3.51.4"},"reference-count":45,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T00:00:00Z","timestamp":1653004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Salamanca","award":["18.KD.7N\/463AC01"],"award-info":[{"award-number":["18.KD.7N\/463AC01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Comorbid diabetes and depression constitutes a major health problem, worsening associated cardiovascular diseases. Fluoxetine\u2019s (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 \u03bcg\/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 \u03bcg\/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.<\/jats:p>","DOI":"10.3390\/ijms23105736","type":"journal-article","created":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T13:56:12Z","timestamp":1653054972000},"page":"5736","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Fluoxetine Treatment Decreases Cardiac Vagal Input and Alters the Serotonergic Modulation of the Parasympathetic Outflow in Diabetic Rats"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6140-4322","authenticated-orcid":false,"given":"M\u00f3nica","family":"Garc\u00eda-Domingo","sequence":"first","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda, Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5252-9470","authenticated-orcid":false,"given":"Jos\u00e9 \u00c1ngel","family":"Garc\u00eda-Pedraza","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda, Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2344-4523","authenticated-orcid":false,"given":"Juan Francisco","family":"Fern\u00e1ndez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda, Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda, Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4810-9673","authenticated-orcid":false,"given":"Mar\u00eda Luisa","family":"Mart\u00edn","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda, Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asunci\u00f3n","family":"Mor\u00e1n","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda, Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s44192-022-00007-0","article-title":"The interface of COVID-19, diabetes, and depression","volume":"2","author":"Steenblock","year":"2022","journal-title":"Discov. 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