Effects of Serotonergic Drugs on Intraluminal Pressure of Vas Deferens Induced by Electrical Stimulation of Rat Hypogastric Nerve

Seo, Kyung Keun; Kwak, Seung Min; Kim, Sae Chul

Abstract

PURPOSE: To compare the effects of various serotonergic drugs on the inhibition of intraluminal pressure rise in the rat vas deferens induced by electrical stimulation of the hypogastric nerve. MATERIAL AND METHODS: Twenty-five Sprague Dawley rats (250-300 gm) were randomly divided into five groups of five animals each, which received intravenous injection of normal saline, clomipramine, sertraline, paroxetine, or fluoxetine. Before (baseline pressure) and 30 minutes after intravenous injection of four different doses (0.1 to 20 the therapeutic dose) of each agent, the hypogastric nerve, identified using microsurgical technique, was electrically stimulated, and the intraluminal pressure of the vas deferens was measured (central effect group). To evaluate the peripheral effects of clomipramine and sertraline, intraluminal vasal pressure was also measured after transection of all proximal sympathetic nerves projecting to the hypogastric nerve and the commissural branches between the right and left major and accessory pelvic ganglia. The adrenal veins were ligated bilaterally.
RESULTS
Repeated stimulation of the hypogastric nerves, anesthesia of long duration (3hours), and repeated intravenous injection of normal saline did not result in significant changes in the intraluminal pressure of the vas deferens in a dose-dependent manner (p<0.05). The extent of inhibition by 20-fold therapeutic doses of clomipramine, sertraline, paroxetine, and fluoxetin were 74.4 1.8%, 34.1 8.3%, 24.8 7.8%, and 8.1 3.5%, respectively. At doses 10- and 20-fold the therapeutic dose, clomipramine had the strongest inhibitory effect, followed by sertraline and paroxetin, then fluoxetine (p<0.05). Definite inhibition was noted in all rats receiving clomipramine at 10- and 20-fold the therapeutic dose; the degree of inhibition was 80% in the sertraline-, 60% in the paroxetine-, and 20% in the fluoxetin-treated group. The inhibitory effect of sertraline on the elevation of the intraluminal vasal pressure in the peripheral-effect group was significantly (p<0.01) less than that in the central-effect group. However, there was no difference in the inhibitory effect of clomipramine in the two groups.
CONCLUSIONS
Clomipramine was the most potent inhibitor of the elevation of the intraluminal pressure of the rat vas after electrical stimulation of the hypogastric nerve. The greater effect might be attributable to an additional peripheral effect of this drug on the vas deferens.