AIMS OF STUDY:
Serotonergic neurons originating in the raphe nuclei descend to the autonomic and somatic nuclei in the lumbosacral spinal cord in rats. There is evidence that these neurons may inhibit the micturition reflex. The receptors in the spinal cord through which this effect is mediated have not been established. 5-HT1A receptor agonists has previously been shown to stimulate micturition in rats when given systemically. 5-HT1A receptors have been shown to be present in the spinal cord (1), the raphe nuclei, as well as the limbic region (2). In the raphe nuclei, 5-HT1A receptor stimulation has profound effect on the spinally descending serotonergic neurons (3), which could influence micturition. To get some insight into the receptor mechanisms involved, we studied the effects of i.v. and i.t. 8-OH-DPAT (a 5-HT1A agonist) and WAY100635 (a 5-HT1A antagonist) as well as 5-HT, in conscious rats undergoing continuous cystometry.

METHODS:
Female Sprague-Dawley rats, weighing 200-250 g, were used. A polyethylene catheter was inserted in the bladder dome and another catheter was inserted into the femoral vein or intrathecally. Three days later continuous cystometry was performed. Micturition parameters were recorded and drug effects were compared to baseline values.

RESULTS:
Administration of 5-HT i.v. (500 nmol.kg-1;n=12) or i.t. (140 nmol.kg-1;n=6) increased significantly micturition pressure and decreased significantly bladder capacity (39±7% i.v.;30±8% i.t.) and micturition volume. 8-OH-DPAT (i.v. 300 nmol.kg-1;n=6; i.t. 30 nmol.kg-1;n=7) had similar effects and significantly decreased bladder capacity (i.v. 54±7%;i.t. 59±9%). WAY 100635, given i.v. (1000 nmol.kg-1;n=9), increased bladder capacity by 27±19% without affecting other cystometric parameters. Administration of WAY100635 i.t. (100 nmol;n=6) did not affect bladder capacity and micturition pressure, but was able to inhibit the effect of intrathecal 8-OH-DPAT.

CONCLUSIONS:
The results show that exogenous 5-HT stimulates micturition when given systemically or intrathecally. The 5-HT1A receptor is probably a mediator of this effect, although other 5-HT receptors might be of importance. The slight inhibitory effect of systemically administered 5-HT1A antagonists on micturition cannot be explained by a peripheral effect (3) or by, as suggested by our findings, stimulation of spinal 5-HT1A receptors. Therefore, supraspinal 5-HT1A receptors may be involved. The stimulating effect of i.t. 5-HT on micturition is in apparent disagreement with the proposed existence of descending serotonergic pathways tonically inhibiting micturition. The importance of spinal 5-HT receptors for micturition, remains to be elucidated.

1) Neuroscience 1993, 55:235-252
2) J. of Neuroscience 1986, 6(12):3474-3482
3) J. of Pharm. Exp. Ther. 1992, 262:181-189