1. Fluoxetine oral treatment discloses 5-HT 1D receptor as vagoinhibitor of the cardiac cholinergic neurotransmission in rat.
- Author
-
López C, Gómez-Roso M, García-Pedraza JÁ, Martín ML, Morán A, and García-Domingo M
- Subjects
- Administration, Oral, Animals, Antidepressive Agents, Second-Generation therapeutic use, Bradycardia etiology, Depression complications, Depression drug therapy, Disease Models, Animal, Drug Evaluation, Preclinical, Fluoxetine therapeutic use, Heart innervation, Heart Rate drug effects, Humans, Oxadiazoles pharmacology, Phenols pharmacology, Rats, Rats, Wistar, Serotonin pharmacology, Serotonin 5-HT1 Receptor Antagonists pharmacology, Serotonin Receptor Agonists metabolism, Sulfonamides pharmacology, Tryptamines pharmacology, Vagus Nerve metabolism, Antidepressive Agents, Second-Generation pharmacology, Bradycardia drug therapy, Fluoxetine pharmacology, Receptor, Serotonin, 5-HT1D metabolism, Vagus Nerve drug effects
- Abstract
Although depression and cardiovascular diseases are related, the role of antidepressants such as fluoxetine (increasing serotonin levels) within cardiac regulation remains unclear. We aimed to determine whether fluoxetine modifies the pharmacological profile of serotonergic influence on vagal cardiac outflow. Rats were treated with fluoxetine (10 mg/kg per day; p.o.) for 14 days or equivalent volumes of drinking water (control group); then, they were pithed and prepared for vagal stimulation. Bradycardic responses were obtained by electrical stimulation of the vagal fibers (3, 6, and 9 Hz) or i.v. acetylcholine (ACh; 1, 5, and 10 μg/kg). The i.v. administration of 5-hydroxytryptamine (5-HT; 10 and 50 μg/kg) inhibited the vagally induced bradycardia. 5-CT (5-HT
1/7 agonist) and L-694,247 (5-HT1D agonist) mimicked the serotonin inhibitory effect while α-methyl-5-HT (5-HT2 agonist) was devoid of any action. SB269970 (5-HT7 antagonist) did not abolish 5-CT inhibitory action on the electrically induced bradycardia. Pretreatment with LY310762 (5-HT1D antagonist) blocked the effects induced by L-694,247 and 5-CT. 5-HT and 5-CT failed to modify the bradycardia induced by exogenous ACh. Our outcomes suggest that fluoxetine treatment modifies 5-HT modulation on heart parasympathetic neurotransmission in rats, evoking inhibition of the bradycardia via prejunctional 5-HT1D in pithed rats.- Published
- 2019
- Full Text
- View/download PDF