Influence of central serotonergic mechanisms on lower urinary tract function.

The effects of serotonergic drugs on the central nervous system control of the lower urinary tract have revealed possible approaches for the treatment of detrusor overactivity and urinary incontinence. Studies in animals of the distribution of serotonergic nerves and receptors and the changes in voiding function induced by serotonin (5-hydroxytryptamine [5-HT]) receptor agonists and antagonists, as well as 5-HT reuptake inhibitors, form a basis for the development of such treatments. In rats and cats, spinal reflex circuits involved in voiding function exhibit a dense serotonergic innervation, multiple 5-HT receptors, and sensitivity to various drugs that affect serotonergic transmission. Although there is some evidence in the rat for serotonergic facilitation of voiding, most experiments in rats and cats indicate that activation of the central serotonergic system by 5-HT reuptake inhibitors, as well as by 5-HT1A and 5-HT2 receptor agonists, depresses reflex bladder contractions and increases the bladder volume threshold for inducing micturition. These data indicate that activation of the central serotonergic system can suppress voiding by enhancing efferent control of the urethral outlet and inhibiting the parasympathetic excitatory input to the urinary bladder. The 5-HT receptors and reuptake mechanisms, therefore, represent targets for the development of new treatments of detrusor overactivity and urinary incontinence.