Fluoxetine oral treatment discloses 5-HT1D receptor as vagoinhibitor of the cardiac cholinergic neurotransmission in rat.

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-HT1/7 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.