The central nervous system is essential for the storage and elimination of urine. This occurs at the level of the sacral spinal cord and supraspinally utilising the autonomic and the somatic nervous system (De Groat, 2006). A major efferent site found in the rostral dorsalateral pons is Barrington’s nucleus (pontine micturition centre; PMC or M region), which sends projections to the parasympathetic preganglionic neurons in the sacral spinal cord projecting to the bladder. Another area located in the region of the ventrolateral parabachial and Kolliker-Fuse nucleus, is known as the L-region (“continence centre”) and sends projections to Onuf’s nucleus in sacral spinal cord, which contains the motoneurons innervating the striated muscles of the urethral sphincter. This region has not been defined in humans or rats (Griffiths, 2002). Afferent pathways terminate in the caudal periaqueductal grey (PAG), which provides the major excitatory inputs to the PMC along with some hypothalamic and preoptic regions. Further, dense projections to this region of the PAG come from orbital and prefontal cortex and regions such as the amygdala and hypothalamus (Holstege, 2005). As would be expected all these pathways utilise the neurotransmitters glutamate and GABA/glycine, for instance NMDA or AMPA antagonists depressed bladder reflexes and sphincter activity (De Groat & Yoshimura, 2001). However other transmitters such as 5 hydroxytryptamine (5 HT; Ramage, 2006), noradrenaline (Michel & Vrydag, 2006), dopamine as well as many others also play a role (De Groat, 2006). In the case of 5-HT blockade of central 5-HT_1A receptors both spinally and supraspinally will increase the threshold for micturition reflex, as does the blockade of supraspinal 5-HT₇ receptors. However once the reflex is initiated the bladder contraction height is similar along with the associated changes in urethral variables. This may suggest that both receptors attenuate afferent input. Surprisingly afferent (pelvic nerve) evoked excitation of the PMC was unaffected by blockade of 5-HT_1A receptors, although other sites need to be tested such as the PAG. Effect of 5-HT₇ blockade has yet to be tested. It is possible that this 5-HT system, at least, supraspinally may control the level at which the PMC neurones switch from storage to expulsion. The PMC does receive a dense innervation from the median raphé, while the dorsal raphé does project to this brain area but it is not clear if this includes the PMC. Interestingly, both these raphé nuclei send projections to the raphé magnus. Electrical stimulation of this nucleus in rats causes inhibition of bladder contractions, although sacral 5 HT_1A receptors do play a physiological role, at least in rat, it is an excitatory role and again probably on the afferent side of the reflex. It could be mediated by 5-HT_2C receptors, as their activation has an inhibitory action, although blockade of these receptors does not affect the micturition reflex. Blockade of 5 HT_2A receptors does cause a small inhibition of the reflex. Further, at the sacral level activation of 5 HT_2A receptors in the rat causes excitation of the external urethral sphincter, again the physiological role of these receptors is far from clear (Mbaki & Ramage, 2008). Interestingly, under certain pathophysiolgical conditions 5-HT_1A receptors have also been shown to excite this sphincter. Again their physiological role in sphincter regulation is unclear. Overall a reduction in spinal content of 5-HT has been shown to inhibit the micturition reflex. Noradrenaline has also been implicated in the control of micturition and in this respect the locus coeruleus is located adjacent to the PMC. Electrical stimulation of the locus coeruleus causes contraction of the bladder in the cat, which is blocked by intrathecal injection of a α₁-adrenoceptor antagonist, prazosin. This has also been confirmed in the rat. Further, destruction of noradrenaline-containing neurones in the locus coeruleus produces bladder hyperactivity. There are no data on if or how the locus coeruleus inputs to the pontine micturition centre, although interestingly both the dorsal and median raphé send and receive projections from the locus coeruleus. However, increasing the levels of both 5-HT and noradrenaline, using duloxetine a selective serotonin (5-HT)-noradrenaline reuptake inhibitor (SSNRI), is effective in the treatment of stress incontinence. In animal models duloxetine has been shown to increase sphincter activity. In conclusion, although the above has focused on 5-HT and noradrenaline, these studies have only begun to elucidate their role in the complex circuitry involved in the regulation of micturition, which also involves many other transmitters.