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Oxytocin is important for social interactions and maternal behaviour. However, little is known about when, where and how oxytocin modulates neural circuits to improve social cognition. Here we show how oxytocin enables pup retrieval behaviour in female mice by enhancing auditory cortical pup call responses. Retrieval behaviour required the left but not right auditory cortex, was accelerated by oxytocin in the left auditory cortex, and oxytocin receptors were preferentially expressed in the left auditory cortex. Neural responses to pup calls were lateralized, with co-tuned and temporally precise excitatory and inhibitory responses in the left cortex of maternal but not pup-naive adults. Finally, pairing calls with oxytocin enhanced responses by balancing the magnitude and timing of inhibition with excitation. Our results describe fundamental synaptic mechanisms by which oxytocin increases the salience of acoustic social stimuli. Furthermore, oxytocin-induced plasticity provides a biological basis for lateralization of auditory cortical processing.
Single- and double-immunostaining techniques were used systematically to study the distribution pattern and neurochemical density of oxytocin-immunoreactive (-ir) neurons in the digestive tract of the guinea pig. Oxytocin immunoreactivity was distributed widely in the guinea pig gastrointestinal tract; 3%, 13%, 17%, 15%, and 10% of ganglion neurons were immunoreactive for oxytocin in the myenteric plexuses of the gastric corpus, jejunum, ileum, proximal colon, and distal colon, respectively, and 36%, 40%, 52%, and 56% of ganglion neurons were immunoreactive for oxytocin in the submucosal plexuses of the jejunum, ileum, proximal colon, and distal colon, respectively. In the myenteric plexus, oxytocin was expressed exclusively in the intrinsic enteric afferent neurons, as identified by calbindin 28 K. In the submucosal plexuses, oxytocin was expressed in non-cholinergic secretomotor neurons, as identified by vasoactive intestinal polypeptide. Oxytocin-ir nerve fibers in the inner circular muscle layer possibly arose from the myenteric oxytocin-ir neurons, and oxytocin-ir nerve fibers in the mucosa possibly arose from both the myenteric and submucosal oxytocin-ir neurons. Thus, oxytocin in the digestive tract might be involved in gastrointestinal tract motility mainly via the regulation of the inner circular muscle and the balance of the absorption and secretion of water and electrolytes.
Document Type:
Reference
Product Catalog Number:
MAB1637
Product Catalog Name:
Anti-Tubulin Antibody, beta III isoform, CT, clone TU-20 (Similar to TUJ1)
Previous research suggests that the nonpeptide oxytocin receptor (OTR) agonist WAY 267,464 may only partly mimic the effects of oxytocin in rodents. The present study further explored these differences and related them to OTR and vasopressin 1a receptor (V(1a) R) pharmacology and regional patterns of c-Fos expression. Binding data for WAY 267,464 and oxytocin were obtained by displacement binding assays on cellular membranes, while functional receptor data were generated by luciferase reporter assays. For behavioural testing, adolescent rats were tested in a social preference paradigm, the elevated plus-maze (EPM) and for locomotor activity changes following WAY 267,464 (10 and 100 mg/kg, i.p.) or oxytocin (0.1 and 1 mg/kg, i.p.). The higher doses were also examined for their effects on regional c-Fos expression. Results showed that WAY 267,464 had higher affinity (K(i) ) at the V(1a) R than the OTR (113 versus 978 nm). However, it had no functional response at the V(1a) R and only a weak functional effect (EC(50) ) at the OTR (881 nm). This suggests WAY 267,464 is an OTR agonist with weak affinity and a possible V(1a) R antagonist. Oxytocin showed high binding at the OTR (1.0 nm) and V(1a) R (503 nm), with a functional EC(50) of 9.0 and 59.7 nm, respectively, indicating it is a potent OTR agonist and full V(1a) R agonist. WAY 267,464 (100 mg/kg), but not oxytocin, significantly increased the proportion of time spent with a live rat, over a dummy rat, in the social preference test. Neither compound affected EPM behaviour, whereas the higher doses of WAY 267,464 and oxytocin suppressed locomotor activity. WAY 267,464 and oxytocin produced similar c-Fos expression in the paraventricular hypothalamic nucleus, central amygdala, lateral parabrachial nucleus and nucleus of the solitary tract, suggesting a commonality of action at the OTR with the differential doses employed. However, WAY 267,464 caused greater c-Fos expression in the medial amygdala and the supraoptic nucleus than oxytocin, and lesser effects in the locus coeruleus. Overall, our results confirm the differential effects of WAY 267,464 and oxytocin and suggest that this may reflect contrasting actions of WAY 267,464 and oxytocin at the V(1a) R. Antagonism of the V(1a) R by WAY 267,464 could underlie some of the prosocial effects of this drug either through a direct action or through disinhibition of oxytocin circuitry that is subject to vasopressin inhibitory influences.
Hypoglossal (XII) motoneurons innervate extrinsic and intrinsic muscles of the tongue and control behaviors such as suckling, swallowing, breathing or chewing. In young rats, XII motoneurons express V1a vasopressin and oxytocin receptors. Previous studies have shown that activation of these receptors induces direct powerful excitation in XII motoneurons. In addition, by activating V1a receptors vasopressin can also enhance inhibitory synaptic transmission in the XII nucleus. In the present work, we have further characterized the effect of these neuropeptides on synaptic transmission in the XII nucleus. We have used brainstem slices of young rats and whole-cell patch clamp recordings. Oxytocin enhanced the frequency of spontaneous inhibitory postsynaptic currents by a factor of two and a half. GABAergic and glycinergic events were both affected. The oxytocin effect was mediated by uterine-type oxytocin receptors. Vasopressin and oxytocin also increased the frequency of excitatory synaptic currents, the enhancement being sixfold for the former and twofold for the latter compound. These effects were mediated by V1a and oxytocin receptors, respectively. Miniature synaptic events were unaffected by either vasopressin or oxytocin. This indicates that the peptide-dependent facilitation of synaptic currents was mediated by receptors located on the somatodendritic membrane of interneurons or premotor neurons, and not by receptors sited on axon terminals contacting XII motoneurons. Accordingly, recordings obtained from non-motoneurons located near the border of the XII nucleus showed that part of these cells possess functional V1a and oxytocin receptors whose activation leads to excitation. Some of these neurons could be antidromically activated following electrical stimulation of the XII nucleus, suggesting that they may act as premotor neurons. We propose that in young rats, oxytocin and vasopressin may function as neuromodulators in brainstem motor circuits responsible of tongue movements.
Oxytocin is released by the posterior pituitary gland during male orgasm. Additionally, the presence of an oxytocin receptor gene and protein expression in human corpus cavernosum is demonstrated, and it has contractile activity on the smooth muscle of the animal and human corpus cavernosum in vitro. The aim of this study was to investigate the immunoreactivity of oxytocin in corpus cavernosum of patients with organic erectile dysfunction and to compare it with healthy controls.
The drug 3,4 methylenedioxymethamphetamine (MDMA; ecstasy) has a widely documented ability to increase feelings of love and closeness toward others. The present study investigated whether oxytocin, a neuropeptide involved in affiliative behavior, may play a role in this effect. A moderate (5 mg/kg, i.p.) dose of MDMA increased social interaction in male Wistar rats, primarily by increasing the amount of time rats spent lying adjacent to each other. MDMA (5 mg/kg) activated oxytocin-containing neurons in the supraoptic and paraventricular nuclei of the hypothalamus, as shown by Fos immunohistochemistry. MDMA (5 mg/kg i.p.) also increased plasma oxytocin levels and this effect was prevented by pre-treatment with the 5-HT(1A) antagonist N-[2-[4-(2-methyoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY 100,635; 1 mg/kg i.p.). The oxytocin receptor antagonist tocinoic acid (20 microg, i.c.v.) had no effect on social behavior when given alone but significantly attenuated the facilitation of social interaction produced by MDMA (5 mg/kg). The 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)-tetraline) (8-OH-DPAT, 0.25 mg/kg, i.p.) increased social behavior in a similar way to MDMA and this effect was also significantly attenuated by tocinoic acid. Taken together, these results suggest that oxytocin release, stimulated by MDMA through 5-HT(1A) receptors, may play a key role in the prosocial effects of MDMA and underlie some of the reinforcing effects of the drug.
Single-minded 1 (Sim1) encodes a transcription factor essential for formation of the hypothalamic paraventricular nucleus (PVN). Sim1 haploinsufficiency is associated with hyperphagic obesity and increased linear growth in humans and mice, similar to the phenotype of melanocortin 4 receptor (Mc4r) mutations. PVN neurons in Sim1(+/-) mice are hyporesponsive to the melanocortin agonist melanotan II. PVN neuropeptides oxytocin (Oxt), TRH and CRH inhibit feeding when administered centrally. Consequently, we hypothesized that altered PVN neuropeptide expression mediates the hyperphagia of Sim1(+/-) mice. To test this hypothesis, we measured hypothalamic expression of PVN neuropeptides in Sim1(+/-) and wild-type mice. Oxt mRNA and peptide were decreased by 80% in Sim1(+/-) mice, whereas TRH, CRH, arginine vasopressin (Avp), and somatostatin mRNAs were decreased by 20-40%. Sim1(+/-) mice also showed abnormal regulation of Oxt but not CRH mRNA in response to feeding state. A selective Mc4r agonist activated PVN Oxt neurons in wild-type mice, supporting involvement of these neurons in melanocortin feeding circuits. To test whether Oxt itself regulates feeding, we measured the effects of central administration of an Oxt receptor antagonist or repeated doses of Oxt on food intake of Sim1(+/-) and wild-type mice. Sim1(+/-) mice were hypersensitive to the orexigenic effect of the Oxt receptor antagonist. Oxt decreased the food intake and weight gain of Sim1(+/-) mice at a dose that did not affect wild-type mice. Our results support the importance of Oxt neurons in feeding regulation and suggest that reduced Oxt neuropeptide is one mechanism mediating the hyperphagic obesity of Sim1(+/-) mice.
Oxytocin induces P19 cells to differentiate into cardiomyocytes possibly through the oxytocin/oxytocin receptor system. We added oxytocin to the growth medium of P19CL6, a subline of P19, but they did not differentiate into cardiomyocytes as indicated by RT-PCR and Western blotting results. During the cardiac commitment time of P19CL6 cells, the mRNA expression levels of the oxytocin receptor were upregulated by the addition of oxytocin as well as DMSO, but an upregulation of Gata4 expression levels was only observed for the cells induced by DMSO. The in silico analysis of the upstream sequence of the oxytocin receptor predicted putative binding sites for Gata4 and Nkx2.5. These results suggest that upregulations of the oxytocin receptor and Gata4 are important for cardiomyocyte differentiation processes.