Excitatory Effect Of Oxytocin Research Articles

Oxytocin activation of paraventricular thalamic neurons promotes feeding motivation to attenuate stress-induced hypophagia.

The neuropeptide oxytocin (OT) regulates important brain functions including feeding through activating OT receptors in multiple brain areas. Both OT fibers and OT receptors have been reported in the paraventricular thalamus (PVT), an area that was revealed to be important for the control of emotion, motivation, and food intake. However, the function and modulation of PVT OT signaling remain unknown. Here, we used a progressive ratio (PR) schedule of reinforcement to examine the role of PVT OT signaling in regulating the motivation for food and patch-clamp electrophysiology to study the modulation of OT on PVT neurons in brain slices. We demonstrate that PVT OT administration increases active lever presses to earn food rewards in both male and female mice under PR trials and OT receptor antagonist atosiban inhibits OT-induced increase in motivated lever presses. However, intra-PVT OT infusion does not affect food intake in normal conditions but attenuates hypophagia induced by stress and anxiety. Using patch-clamp recordings, we find OT induces long-lasting excitatory effects on neurons in all PVT regions, especially the middle to posterior PVT. OT not only evokes tonic inward currents but also increases the frequency of spontaneous excitatory postsynaptic currents on PVT neurons. The excitatory effect of OT on PVT neurons is mimicked by the specific OT receptor agonist [Thr4, Gly7]-oxytocin (TGOT) and blocked by OT receptor antagonist atosiban. Together, our study reveals a critical role of PVT OT signaling in promoting feeding motivation to attenuate stress-induced hypophagia through exciting PVT neurons.

Role of Connexin 36 in Autoregulation of Oxytocin Neuronal Activity in Rat Supraoptic Nucleus.

In the supraoptic nucleus (SON), the incidence of dye coupling among oxytocin (OT) neurons increases significantly in nursing mothers. However, the type(s) of connexin (Cx) involved is(are) unknown. In this study, we specifically investigated whether Cx36 plays a functional role in the coupling between OT neurons in the SON of lactating rats. In this brain region, Cx36 was mainly coimmunostained with vasopressin neurons in virgin female rats, whereas in lactating rats, Cx36 was primarily colocalized with OT neurons. In brain slices from lactating rats, application of quinine (0.1 mM), a selective blocker of Cx36, significantly reduced dye coupling among OT neurons as well as the discharge/firing frequency of spikes/action potentials and their amplitude, and transiently depolarized the membrane potential of OT neurons in whole-cell patch-clamp recordings. However, quinine significantly reduced the amplitude, but not frequency, of inhibitory postsynaptic currents in OT neurons; the duration of excitatory postsynaptic currents was reduced but not their frequency and amplitude. Furthermore, the excitatory effect of OT (1 pM) on OT neurons was significantly weakened and delayed by quinine, and burst firing was absent in the presence of this inhibitor. Lastly, Western blotting analysis revealed that the presence of combined, but not alone, quinine and OT significantly reduced the amount of Cx36 in the SON. Thus, Cx36-mediated junctional communication plays a crucial role in autoregulatory control of OT neuronal activity, likely by acting at the postsynaptic sites. The level of Cx36 is modulated by its own activity and the presence of OT.

Estradiol upregulates the expression of oxytocin receptor in colon in rats

The study was designed to investigate the effect of estradiol on the excitatory effect of oxytocin (OT) on colon motility. Female Wistar rats were used, and some of them were ovariectomized (OVX) and treated with vehicle or estradiol (E(2)). A plastic balloon made of condom was inserted into colon to monitor the change of colonic pressure in vivo. Longitudinal muscle strips of distal colon were prepared to monitor the spontaneous contraction of colon in vitro. Expression of OT receptor (OTR) was investigated by Western blot analysis. Expression of OTR mRNA was detected by RT-PCR. Immunohistochemistry was used to locate OTR. In OVX rats, pretreatment of E(2) (4-100 microg/kg sc) dose-dependently increased the excitatory effect of OT on colon motility both in vivo and in vitro and increased the expression of OTR and OTR mRNA in colon. Systemic administration of OT excited the colon motility in vivo in rats at perioda of proestrus and estrus but did not influence it at diestrus period, when the concentration of plasma E(2) was lowest in the estrous cycle. Pretreatment of atosiban, the specific OTR antagonist, and TTX, the blocker of voltage-dependent sodium channel on nerve fiber, attenuated the excitatory effect of OT on colon motility. OTR was located in myenteric plexus of colon. These results suggested that E(2) increased the excitatory effect of OT on colon motility by upregulating the expression of OTR in myenteric plexus.

Excitatory effects of oxytocin and cholecystokinin on oxytocin neurones: differences between virgin, pregnant and lactating rats

Extracellular recordings were made from supraoptic oxytocin (OT) neurones in rat brain slices to investigate the effect of reproductive state on their excitation by OT and cholecystokinin (CCK). Stable background activity was induced by local glutamate application, and OT neurones were identified by their continuous firing and opioid inhibition. The excitatory effect of OT (indicated by percentage neurones excited, peak increment in firing, and response magnitude) was maximal in lactating rats, intermediate in virgin, and lowest in pregnant animals. Excitation by CCK was high in both lactating and virgin rats but, as with OT tests, was minimal in the pregnant group. These adaptations in the responses to OT and CCK may help to ensure that the firing of OT neurones is appropriately regulated to meet changing demands for OT release.

Modification by magnesium of the excitatory effect of oxytocin on electrical and mechanical activities of pregnant human myometrium

Modification by magnesium of the excitatory effect of oxytocin on electrical and mechanical activities of pregnant human myometrium

Oxytocin excites neurones in the bed nucleus of the stria terminalis of the lactating rat in vitro

Unit recordings were made in the bed nucleus of the stria terminalis in brain slices obtained from lactating rats. Addition of 10 −8 to 10 −6 M oxytocin to the perifusate caused a reversible and repeatable excitation in 28/53 (53%) of neurones. The excitatory effect of oxytocin was completely blocked in the presence of the antagonist [d(CH 2) 5 d-Tyr(OEt) 2,Val 4,Cit 8]vasopressin (5 × 10 −7M) and a smaller excitation was achieved with equimolar concentration of arginine vasopressin, implicating the involvement of an oxytocin receptor. This effect is discussed in relation to the actions of centrally administered oxytocin in the lactating rat.

Neurohypophysial hormones: Neuronal effects in autonomic and limbic areas of the rat brain.

The neuropeptides vasopressin and oxytocin were first characterized as hormones, i. e., signalling molecules which are synthesized in hypothalamic neurones, transported toward the neurohypophysis and from there secreted into the general circulation. Although extrahypophysial Gomori-positive pathways were described in the brain as early as the mid-1950s, it is only during the last decade that the neurotransmitter role of vasopressin and oxytocin has begun to be investigated. Recent electrophysiological and morphological studies from our laboratory are summarized. Using extracellular and intracellular recordings from in vitro brain slices, a direct excitatory action of vasopressin was demonstrated in the lateral septum and in the nucleus of the solitary tract. This action of vasopressin was mediated by V1-type receptors. An excitatory effect of oxytocin, mediated by receptors similar to those present in uterus, has also been found in the dorsal motor nucleus of the vagus nerve. In accordance with these results, light microscopic autoradiography showed the presence in these brain areas of high affinity binding sites for vasopressin and for oxytocin, respectively. While these data corroborate the notion that vasopressin and oxytocin are probably involved in interneuronal communications, several questions, however, remain. The membrane mechanism by which vasopressin and oxytocin cause neuronal excitation is still unknown and evidence that endogenous vasopressin and oxytocin act at central synapses deserves further investigation.

Effects of PGE2 and PGF2α on the simulation by noradrenaline and oxytocin of human cervical muscle activity at term

Cervical specimens were obtained by needle biopsy in connection with caesarean section at term pregnancy. The preparations were superfused in an organ chamber and contractions were registered isometrically. Prostaglandin (PG) E2 and F2 alpha inhibited spontaneous contractions. The stimulatory action of noradrenaline was not influenced by PGF2 alpha but was reduced by PGE2 whereas both PGs abolished the excitatory effect of oxytocin.

Effects of magnesium, oxytocin, and prostaglandin F2 alpha on the generation and propagation of excitation in the longitudinal muscle of rat myometrium during late pregnancy.

In order to find out the changes in myometrial properties towards parturition, effects of Mg, oxytocin, and prostaglandin F2 alpha (PGF2 alpha) were investigated on longitudinal muscle strips taken from rat uteri on Days 20 and 22 of pregnancy. With intracellular recording by microelectrode, membrane potential was 50.5 +/- 1.4 mV on Day 20, and 49.9 +/- 1.0 mV on Day 22 in the Mg-free Krebs solution. The slow potential was larger, and the spike potentials during a burst discharge exhibited variable amplitude on Day 20, whereas these were regular on Day 22. With extracellular recording by the rubber gap method, spike potentials discharged in a synchronized manner on Day 22, suggesting a better coordination between cell groups. When 1.2 mM Mg was applied, the spontaneous activity was depressed more strongly on Day 22. The excitatory effect of PGF2 alpha faded sooner, whereas that of oxytocin persisted. When the fading of PGF2 alpha had occurred, the excitatory effect of oxytocin was weaker than when it was given alone. Because propagation of spontaneous activity, occurring either in the Mg-free solution or in the presence of oxytocin and PGF2 alpha in normal Krebs solution, did not show a definite direction from ovarian to vaginal side of the longitudinal muscle, it was concluded that generation of spontaneous activity was not localized in a given site of the muscle, but originated anywhere in Days 20 and 22 preparations.

Modification by magnesium and manganese ions of the effects of oxytocin on the electrical and mechanical activity of the longitudinal muscle of estrogen-treated rat uterus.

Ovariectomized rats were given one-shot injections of 10 microgram estradiol-17 beta benzoate, and the longitudinal muscle of the uterus was used for experiment 4 days later. The membrane potential was 58.8 +/- 2.4 mV, and the membrane activity consisted of repetitive spike potentials carried on a plateau potential. Oxytocin (1 mU/ml) caused a depolarization of 7.6 +/- 3.7 mV in a Mg-free Locke solution, a prolongation of burst discharge and increase in the frequency of spontaneous activity. The effects were potentiated by 1-3 mM Mg. Burst discharge was abolished by the application of 0.5 mM Mn, and resumed when 0.1 mU/ml oxytocin was applied. Depolarization up to about - 30 mV and a contracture were caused by 1 mU oxytocin when applied with 1-2 mM Mn. The excitatory effect of oxytocin was depressed by 5 mM Mn. Marked depolarization and contracture were produced by 1 mU oxytocin when the application of Mn was discontinued (rebound phenomenon). The above observations indicate the superficial site of Mg and Mn at low concentration in cooperative action with oxytocin, and an additional site of Mn for the rebound potentiation of contraction and depolarization. It is proposed that oxytocin accelerated Mn influx, and that intracellular Mn participates in electrical and contractile responses due to the application of oxytocin. In this respect, acetylcholine caused a similar effect.