Benoussaidh, Anissa, Yves Maurin, and Olivier Rampin. Spinal effects of oxytocin on uterine motility in anesthetized rats. Am J Physiol Regul Integr Comp Physiol 287: R446 -R453, 2004. First published March 25, 2004 10.1152/ajpregu.00117.2004.-The rat uterus receives an innervation from the lumbosacral and thoracolumbar segments of the spinal cord. These segments receive descending oxytocinergic projections from the paraventricular nucleus of the hypothalamus. We tested the hypothesis that oxytocin regulates uterine motility through a spinal site of action. Oxytocin was administered in anesthetized female rats either intrathecally at the lumbosacral or thoracolumbar spinal cord levels or intravenously. Uterine activity was revealed by measuring changes of intrauterine pressure using an indwelling balloon placed in one caudal uterine horn. The uterus displayed a spontaneous activity characterized by intrauterine pressure rises, the frequency, amplitude, and duration of which were dependent on the stage of the estrous cycle. Oxytocin delivered at the lumbosacral level affected the frequency (during proestrus, estrus, and diestrus) and amplitude (during proestrus and estrus) of uterine activity. During estrus, oxytocin delivered at the thoracolumbar level affected the frequency, amplitude, and duration of the intrauterine pressure rises. Intravenous oxytocin not only affected intrauterine pressure rises (namely amplitude during proestrus and estrus and frequency and duration during estrus) but also increased the basal tone during estrus. The effects of lumbosacral oxytocin were partly mimicked by the oxytocin agonist [Thr 4 ,Gly 7 ]-oxytocin blocked by the oxytocin receptor antagonist atosiban and by hexamethonium. Arginine vasopressin delivered at the lumbosacral level had no effect. These results support our hypothesis that oxytocin released by descending paraventriculo-spinal pathways and acting on spinal oxytocin receptors modulates the activity of the uterus. This regulation is cycle dependent. urogenital; lumbosacral spinal cord; sexual reflexes OXYTOCIN (OT) exerts peripheral contractile effects on the uterus after its release into the systemic circulation by magnocellular neurons of the paraventricular nucleus (29). In addition to this endocrine mode of action, OT may also be released at various levels of the brain stem and spinal cord by paraventriculo-spinal projections originating in parvocellular neurons of the paraventricular nucleus (5,25,28,30,31,33). In the brain stem, this pathway activates motoneurons of the dorsal motor nucleus of the vagus to increase gut motility (6). In the dorsal horn of the spinal cord, OT has been suggested to have antinociceptive effects through the modulation of glutamate release (13). At the lumbosacral level, this pathway has been shown to elicit penile erection in male rats (8) and to participate in the control of bladder activity in female rats (19). Whether OT released at the lumbosacral level affects uterine motility (and to what extent) remained to be shown.Uteri...

The central nervous system contains the nuclei at the origin of autonomic and neuroendocrine pathways to the uterus. Although the anatomical basis of these pathways is known, the conditions of their recruitment and their interactions in the context of copulation remain to be explored. We tested the hypothesis that some central mechanisms could simultaneously recruit both pathways to the uterus. In this aim, we recorded intrauterine pressure changes in anesthetized female rats at the estrus stage after intracerebroventricular (ICV) administration of oxytocin (OT). Doses of 0.3-300 ng elicited increases of frequency and amplitude of uterine contractions. These effects were partly mimicked by the OT agonist [Thr(4),Gly(7)]OT but not by arginine vasopressin. They were blocked by the OT receptor antagonist atosiban delivered either ICV or intravenously. The latter suggests that ICV OT activated the systemic release of OT. The effects of OT were also blocked by hexamethonium, a ganglionic blocking agent, by atropine, a muscarinic receptor antagonist, and by N(omega)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthesis. The results reveal that ICV OT recruits autonomic efferent pathways to the uterus. These results support our hypothesis that the activation of central nuclei can promote uterine contractility, and that OT may be a central coordinator of autonomic and neuroendocrine pathways. The hypothalamus, the source of direct OT-ergic projections to the pituitary, the brain stem, and the spinal cord, may be a target of central OT.