Alterations of Central Hypercapnic Respiratory Response Induced by Acute Central Administration of Serotonin Re-Uptake Inhibitor, Fluoxetine

10.4077/CJP.2011.AMM061

Sahin Gulderen；Guner Ibrahim；Yelmen Nermin；Yaman Onur；Mengi Murat；Simsek Gonul；Sipahi Sevtap

Acute central fluoxetine ； serotonin ； hypercapnic ventilatory response ； ketanserin

The Chinese Journal of Physiology

54卷5期（2011 / 10 / 01）

54 - 64

英文

Long-term neurochemical changes are responsible for therapeutic actions of fluoxetine. The role of increased central concentration of serotonin by inhibiting its re-uptake via fluoxetine on the central hypercapnic ventilatory response is complex and little is known. We aimed to research the effect of acute intracerebroventricular (ICV) injection of fluoxetine on hypercapnic ventilatory response in the absence of peripheral chemoreceptor impulses and the role of 5-HT2 receptors on responses. Eighteen anesthetized albino rabbits were divided as Fluoxetine and Ketanserin groups. For ICV administration of fluoxetine and ketanserin, a cannula was placed in the left lateral ventricle by the stereotaxic method. Respiratory frequency (f(subscript R)), tidal volume (V(subscript T)) and ventilation minute volume (V(subscript E)) were recorded in both groups. ICV fluoxetine (10.12 mMol/kg) injection during normoxia caused significant increases in V(subscript T) and V(subscript E) (both P ＜ 0.01) in the fluoxetine group. When the animals were switched to hypercapnia f/min, V(subscript T) and V(subscript E) increased significantly. The increases in percentage values in V(subscript T) and VE in Fluoxetine + Hypercapnia phase were higher than those during hypercapnia alone (P ＜ 0.01 and P ＜ 0.05, respectively). On blocking of 5-HT2 receptors by ketanserin (0.25 mMol/kg), the ventilatory response to Fluoxetine was abolished and the degree of increases in V(subscript T) and V(subscript E) in the Ketanserin + Hypercapnia phase were lower than those during hypercapnia alone (P ＜ 0.01 and P ＜ 0.001, respectively). We concluded that acute central fluoxetine increases normoxic ventilation and also augments the stimulatory effect of hypercapnia on respiratory neuronal network by 5-HT2 receptors in the absence of peripheral chemoreceptor impulses.

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