Oral fluoxetine treatment changes serotonergic sympatho-regulation in experimental type 1 diabetes.

Abstract

AIMS:

This study investigated whether fluoxetine treatment changes the 5-HT regulation on vascular sympathetic neurotransmission in type 1 diabetes.

MAIN METHODS:

Four-week diabetes was obtained by a single alloxan s.c. administration in male Wistar rats, administering fluoxetine for 14 days (10 mg/kg/day; p.o.). Systolic blood pressure, heart rate, glycaemia, body weight (BW) evolution, creatinine, and blood urea nitrogen (BUN) were monitored. Afterward, rats were pithed to perform the vascular sympathetic stimulation. 5-HT1A/1D/2A receptors expression was analysed by Western blot in thoracic aorta. Both i.v. norepinephrine and the electrical stimulation of the spinal sympathetic drive evoked vasoconstrictor responses.

KEY FINDINGS:

Fluoxetine treatment significantly reduced the BW gain, hyperglycaemia, creatinine, and BUN in diabetic rats. The electrical-produced vasopressor responses were greater in untreated than in fluoxetine-treated diabetic rats. 5-HT decreased the sympathetic-produced vasopressor responses. While 5-CT, 8-OH-DPAT and L-694,247 (5-HT1/7, 5-HT1A and 5-HT1D agonists, respectively) reproduced 5-HT-evoked inhibition, the 5-HT2 activation by α-methyl-5-HT augmented the vasoconstrictions. The 5-CT sympatho-inhibition was reversed by 5-HT1A plus 5-HT1D antagonists (WAY-100,635 and LY310762, respectively), whereas ritanserin (5-HT2A antagonist) blocked the α-methyl-5-HT potentiating effect. Norepinephrine-generated vasoconstrictions were increased or diminished by α-methyl-5-HT or 5-CT, respectively. 5-HT1A/1D/2A receptors were expressed at vascular level, being 5-HT1A expression increased by fluoxetine in diabetic rats.

SIGNIFICANCE:

Our findings suggest that fluoxetine improves metabolic and renal profiles, changes the vasopressor responses, and 5-HT receptors modulating sympathetic activity in diabetic rats: 5-HT1A/1D are involved in the sympatho-inhibition, while 5-HT2A is implicated in the sympatho-potentiation, being both effects pre and/or postjunctional in nature.

• Authors: José Ángel García-Pedraza, Juan Francisco Fernández-González, Cristina López, María Luisa Martín, Claudia Alarcón-Torrecillas, Alicia Rodríguez-Barbero, Asunción Morán, Mónica García-Domingo
• Journal: Life sciences (Life Sci) Vol. 293 Pg. 120335 (Mar 15 2022) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 35051421 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Receptors, Serotonin
• Serotonin Antagonists
• Serotonin Uptake Inhibitors
• Fluoxetine
• Serotonin

Topics

• Administration, Oral
• Animals
• Blood Pressure (drug effects, physiology)
• Diabetes Mellitus, Experimental (drug therapy, metabolism)
• Diabetes Mellitus, Type 1 (drug therapy, metabolism)
• Fluoxetine (administration & dosage)
• Male
• Rats
• Rats, Wistar
• Receptors, Serotonin (metabolism)
• Serotonin (metabolism)
• Serotonin Antagonists (pharmacology)
• Selective Serotonin Reuptake Inhibitors (administration & dosage)