SEROTONERGIC MODULATION OF SPINAL ASCENDING ACTIVITY AND SACRAL REFLEX ACTIVITY EVOKED BY PELVIC NERVE-STIMULATION IN CATS

Serotonin (5-HT) may be inhibitory to micturition at a spinal level. A potential mechanism of action for serotonergic inhibition of bladder function is a depression of the ascending limb of the supraspinal refl ex mediating micturition. Ascending activity evoked by pelvic nerve st imulation was recorded in the thoracic spinal cord of anesthetized cat s. For comparison, spinal reflex activity evoked by pelvic nerve stimu lation was recorded on the pudendal nerve. The effects of intrathecal administration of serotonergic agents were examined to determine wheth er spinal and supraspinal responses to bladder afferent activation wer e modulated by 5-HT. Methysergide (60 nmol), a non-selective serotoner gic antagonist, increased ascending activity by 61 +/- 7% and depresse d spinal reflex activity by 38 +/- 6%. Zatosetron (10 nmol), a 5-HT3 a ntagonist had a similar effect on both activities (increased by 93 +/- 24% and decreased by 77 +/- 7%, respectively). The effect on ascendin g activity of blocking 5-HT, receptors was also confirmed with ICS 205 930 and MDL 72222. 2-Methyl-5-HT (800 nmol), a 5-HT3 agonist, depresse d ascending activity to 46 +/- 9% of control, but enhanced spinal refl ex activity by 73 +/- 92%. These results demonstrate that stimulation of 5-HT3 and methysergide-sensitive 5-HT receptors can inhibit ascendi ng activity and facilitate spinal reflex activity elicited by activati on of bladder afferents. It is suggested that descending serotonergic pathways may participate in the spinal coordination of urinary contine nce. (C) 1998 Elsevier Science B.V. All rights reserved.