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Brain Structure & Function Mar 2023The nonapeptide system modulates numerous social behaviors through oxytocin and vasopressin activation of the oxytocin receptor (OXTR) and vasopressin receptor (AVPR1A)...
The nonapeptide system modulates numerous social behaviors through oxytocin and vasopressin activation of the oxytocin receptor (OXTR) and vasopressin receptor (AVPR1A) in the brain. OXTRs and AVPR1As are widely distributed throughout the brain and binding densities exhibit substantial variation within and across species. Although OXTR and AVPR1A binding distributions have been mapped for several rodents, this system has yet to be characterized in the spiny mouse (Acomys cahirinus). Here we conducted receptor autoradiography and in situ hybridization to map distributions of OXTR and AVPR1A binding and Oxtr and Avpr1a mRNA expression throughout the basal forebrain and midbrain of male and female spiny mice. We found that nonapeptide receptor mRNA is diffuse throughout the forebrain and midbrain and does not always align with OXTR and AVPR1A binding. Analyses of sex differences in brain regions involved in social behavior and reward revealed that males exhibit higher OXTR binding densities in the lateral septum, bed nucleus of the stria terminalis, and anterior hypothalamus. However, no association with gonadal sex was observed for AVPR1A binding. Hierarchical clustering analysis further revealed that co-expression patterns of OXTR and AVPR1A binding across brain regions involved in social behavior and reward differ between males and females. These findings provide mapping distributions and sex differences in nonapeptide receptors in spiny mice. Spiny mice are an excellent organism for studying grouping behaviors such as cooperation and prosociality, and the nonapeptide receptor mapping here can inform the study of nonapeptide-mediated behavior in a highly social, large group-living rodent.
Topics: Animals; Female; Male; Receptors, Oxytocin; RNA, Messenger; Basal Forebrain; Mesencephalon; Oxytocin; Receptors, Vasopressin; Vasopressins; Social Behavior; Murinae
PubMed: 36271259
DOI: 10.1007/s00429-022-02581-z -
Biomedicine & Pharmacotherapy =... Apr 2023Ketamine is a widely used anesthetic with N-methyl-D-aspartate (NMDA) receptor antagonism. Exposure to ketamine and NMDA receptor antagonists may induce psychosis....
Ketamine is a widely used anesthetic with N-methyl-D-aspartate (NMDA) receptor antagonism. Exposure to ketamine and NMDA receptor antagonists may induce psychosis. However, the mechanism underlying the effects of ketamine on the immature brain remains unclear. In this study, NMDA receptor antagonists, ketamine and methoxetamine, were administered to pregnant F344 rats (E17). These regimens induce psychosis-like behaviors in the offspring, such as hyperlocomotion induced by MK-801, a non-competitive NMDA receptor antagonist. We also observed that prepulse inhibition (PPI) was significantly reduced. Interestingly, ketamine administration increased the arginine vasopressin receptor 1A (Avpr1a) expression levels in the striatum of offspring with abnormal behaviors. Methoxetamine, another NMDA receptor antagonist, also showed similar results. In addition, we demonstrated a viral vector-induced Avpr1a overexpression in the striatum-inhibited PPI. In the striatum of offspring, ketamine or methoxetamine treatment increased glutamate decarboxylase 67 (GAD67) and δ-aminobutyric acid (GABA) levels. These results show that prenatal NMDA receptor antagonist treatment induces GABAergic neuronal dysfunction and abnormalities in sensorimotor gating via regulating Avpr1a expression in the striatum.
Topics: Rats; Animals; Pregnancy; Female; Ketamine; Prepulse Inhibition; Receptors, Vasopressin; Receptors, N-Methyl-D-Aspartate; Rats, Inbred F344; Dizocilpine Maleate
PubMed: 36738499
DOI: 10.1016/j.biopha.2023.114318 -
ENeuro 2022Oxytocin (Oxt) controls reproductive physiology and various kinds of social behaviors, but the exact contribution of Oxt to different components of parental care still...
Oxytocin (Oxt) controls reproductive physiology and various kinds of social behaviors, but the exact contribution of Oxt to different components of parental care still needs to be determined. Here, we illustrate the neuroanatomical relations of the parental nurturing-induced neuronal activation with magnocellular Oxt neurons and fibers in the medial preoptic area (MPOA), the brain region critical for parental and alloparental behaviors. We used genetically-targeted mouse lines for , (), (), (), and () to systematically examine the role of Oxt-related signaling in pup-directed behaviors. The -- triple knock-out (TKO), and --- quadruple KO (QKO) mice were grossly healthy and fertile, except for their complete deficiency in milk ejection and modest deficiency in parturition secondary to maternal loss of the or gene. In our minimal stress conditions, pup-directed behaviors in TKO and QKO mothers and fathers, virgin females and males were essentially indistinguishable from those of their littermates with other genotypes. However, KO virgin females did show decreased pup retrieval in the pup-exposure assay performed right after restraint stress. This stress vulnerability in the KO was abolished by the additional KO. The general stress sensitivity, as measured by plasma cortisol elevation after restraint stress or by the behavioral performance in the open field (OF) and elevated plus maze (EPM), were not altered in the KO but were reduced in the KO females, indicating that the balance of neurohypophysial hormones affects the outcome of pup-directed behaviors.
Topics: Animals; Female; Male; Mice; Neurons; Oxytocin; Parturition; Pregnancy; Receptors, Oxytocin; Social Behavior
PubMed: 35017259
DOI: 10.1523/ENEURO.0405-21.2022 -
Current Hypertension Reports Mar 2018In many instances, the renin-angiotensin system (RAS) and the vasopressinergic system (VPS) are jointly activated by the same stimuli and engaged in the regulation of... (Review)
Review
PURPOSE OF REVIEW
In many instances, the renin-angiotensin system (RAS) and the vasopressinergic system (VPS) are jointly activated by the same stimuli and engaged in the regulation of the same processes.
RECENT FINDINGS
Angiotensin II (Ang II) and arginine vasopressin (AVP), which are the main active compounds of the RAS and the VPS, interact at several levels. Firstly, Ang II, acting on AT1 receptors (AT1R), plays a significant role in the release of AVP from vasopressinergic neurons and AVP, stimulating V1a receptors (V1aR), regulates the release of renin in the kidney. Secondly, Ang II and AVP, acting on AT1R and V1aR, respectively, exert vasoconstriction, increase cardiac contractility, stimulate the sympathoadrenal system, and elevate blood pressure. At the same time, they act antagonistically in the regulation of blood pressure by baroreflex. Thirdly, the cooperative action of Ang II acting on AT1R and AVP stimulating both V1aR and V2 receptors in the kidney is necessary for the appropriate regulation of renal blood flow and the efficient resorption of sodium and water. Furthermore, both peptides enhance the release of aldosterone and potentiate its action in the renal tubules. In this review, we (1) point attention to the role of the cooperative action of Ang II and AVP for the regulation of blood pressure and the water-electrolyte balance under physiological conditions, (2) present the subcellular mechanisms underlying interactions of these two peptides, and (3) provide evidence that dysregulation of the cooperative action of Ang II and AVP significantly contributes to the development of disturbances in the regulation of blood pressure and the water-electrolyte balance in cardiovascular diseases.
Topics: Angiotensin II; Animals; Arginine Vasopressin; Blood Pressure; Cardiovascular Diseases; Humans; Receptors, Vasopressin; Renin-Angiotensin System; Water-Electrolyte Balance
PubMed: 29556787
DOI: 10.1007/s11906-018-0823-9 -
American Journal of Physiology. Renal... Nov 2018The antidiuretic hormone vasopressin (VP) is produced by the hypothalamus and is stored and secreted from the posterior pituitary. VP acts via VP type 2 receptors (V2Rs)... (Review)
Review
The antidiuretic hormone vasopressin (VP) is produced by the hypothalamus and is stored and secreted from the posterior pituitary. VP acts via VP type 2 receptors (V2Rs) on the basolateral membrane of principal cells of the collecting duct (CD) to regulate fluid permeability. The VP-evoked endocrine pathway is essential in determining urine concentrating capability. For example, a defect in any component of the VP signaling pathway can result in polyuria, polydipsia, and hypotonic urine, collectively termed diabetes insipidus (DI). A lack of VP production precipitates central diabetes insipidus (CDI), which can be managed effectively by VP supplementation. A majority of cases of nephrogenic diabetes insipidus (NDI) result from V2R mutations that impair receptor sensitivity. No specific therapy is currently available for management of NDI. Evidence is evolving that (pro)renin receptor (PRR), a newly identified member of the renin-angiotensin system, is capable of regulating VP production and action. As such, PRR should be considered strongly as a therapeutic target for treating CDI and NDI. The current review will summarize recent advances in understanding the physiology of renal and central PRR as it relates to the two types of DI.
Topics: Animals; Antidiuretic Agents; Diabetes Insipidus; Diuresis; Genetic Predisposition to Disease; Humans; Kidney; Mutation; Phenotype; Receptors, Cell Surface; Receptors, Vasopressin; Renin-Angiotensin System; Vasopressins; Prorenin Receptor
PubMed: 30019932
DOI: 10.1152/ajprenal.00266.2018 -
Biomedicine & Pharmacotherapy =... Sep 2023The vasopressin system has emerged as a therapeutic focus for lowering portal hypertension and reducing splanchnic vasodilation in patients with refractory ascites....
Partial vasopressin 1a receptor agonism reduces portal hypertension and hyperaldosteronism and induces a powerful diuretic and natriuretic effect in rats with cirrhosis and ascites.
The vasopressin system has emerged as a therapeutic focus for lowering portal hypertension and reducing splanchnic vasodilation in patients with refractory ascites. Clinically available vasopressin agonists are limited by preferential selectivity for V1 receptors that also have steep concentration-response curves with potential risks of excess vasoconstriction and/or complete antidiuretic effects. OCE-205 is a novel, selective, partial V1a receptor agonist with mixed agonist/antagonist activity and no V2 receptor activation at therapeutic doses. We carried out two studies assessing the in vivo effects of OCE-205 in different rat models of cirrhosis and ascites. In a carbon tetrachloride rat cirrhosis model, OCE-205 administration produced a marked reduction in portal hypertension and hyperaldosteronism, along with robust diuretic and natriuretic effects. These effects were accompanied by marked decreases in ascites volume, with three of five animals experiencing total mobilization of ascites. There was no evidence of fluid overload or sodium or water retention, confirming OCE-205's lack of V2 receptor activity. In a second, corroborative study using a bile duct ligation rat model of ascites, OCE-205 produced significant decreases in ascites volume and body weight and a significant increase in urine volume versus vehicle. Urine sodium excretion increased significantly after the first administration of OCE-205 relative to vehicle; however, repeat administration over 5 days did not lead to hyponatremia. Thus, in separate in vivo models, the mixed agonist/antagonist OCE-205 demonstrated relevant and expected endpoint findings consistent with its known mechanism of action and in vitro pharmacology without apparent unwanted effects or nonspecific toxicities.
Topics: Rats; Animals; Diuretics; Natriuretic Agents; Ascites; Vasopressins; Liver Cirrhosis; Sodium; Receptors, Vasopressin; Hypertension, Portal; Hyperaldosteronism
PubMed: 37418980
DOI: 10.1016/j.biopha.2023.115116 -
International Journal of Molecular... Jan 2023Stroke is a life-threatening condition in which accurate diagnoses and timely treatment are critical for successful neurological recovery. The current acute treatment... (Review)
Review
Stroke is a life-threatening condition in which accurate diagnoses and timely treatment are critical for successful neurological recovery. The current acute treatment strategies, particularly non-invasive interventions, are limited, thus urging the need for novel therapeutical targets. Arginine vasopressin (AVP) receptor antagonists are emerging as potential targets to treat edema formation and subsequent elevation in intracranial pressure, both significant causes of mortality in acute stroke. Here, we summarize the current knowledge on the mechanisms leading to AVP hyperexcretion in acute stroke and the subsequent secondary neuropathological responses. Furthermore, we discuss the work supporting the predictive value of measuring copeptin, a surrogate marker of AVP in stroke patients, followed by a review of the experimental evidence suggesting AVP receptor antagonists in stroke therapy. As we highlight throughout the narrative, critical gaps in the literature exist and indicate the need for further research to understand better AVP mechanisms in stroke. Likewise, there are advantages and limitations in using copeptin as a prognostic tool, and the translation of findings from experimental animal models to clinical settings has its challenges. Still, monitoring AVP levels and using AVP receptor antagonists as an add-on therapeutic intervention are potential promises in clinical applications to alleviate stroke neurological consequences.
Topics: Animals; Arginine Vasopressin; Vasopressins; Stroke; Nervous System Diseases; Antidiuretic Hormone Receptor Antagonists; Arginine; Glycopeptides
PubMed: 36768443
DOI: 10.3390/ijms24032119 -
Scientific Reports Feb 2021Contemporary theory that emphasizes the roles of oxytocin and vasopressin in mammalian sociality has been shaped by seminal vole research that revealed interspecific...
Contemporary theory that emphasizes the roles of oxytocin and vasopressin in mammalian sociality has been shaped by seminal vole research that revealed interspecific variation in neuroendocrine circuitry by mating system. However, substantial challenges exist in interpreting and translating these rodent findings to other mammalian groups, including humans, making research on nonhuman primates crucial. Both monogamous and non-monogamous species exist within Eulemur, a genus of strepsirrhine primate, offering a rare opportunity to broaden a comparative perspective on oxytocin and vasopressin neurocircuitry with increased evolutionary relevance to humans. We performed oxytocin and arginine vasopressin 1a receptor autoradiography on 12 Eulemur brains from seven closely related species to (1) characterize receptor distributions across the genus, and (2) examine differences between monogamous and non-monogamous species in regions part of putative "pair-bonding circuits". We find some binding patterns across Eulemur reminiscent of olfactory-guided rodents, but others congruent with more visually oriented anthropoids, consistent with lemurs occupying an 'intermediary' evolutionary niche between haplorhine primates and other mammalian groups. We find little evidence of a "pair-bonding circuit" in Eulemur akin to those proposed in previous rodent or primate research. Mapping neuropeptide receptors in these nontraditional species questions existing assumptions and informs proposed evolutionary explanations about the biological bases of monogamy.
Topics: Animals; Biological Evolution; Brain; Brain Mapping; Evolution, Molecular; Female; Lemuridae; Male; Memory; Neurosecretory Systems; Oxytocin; Pair Bond; Primates; Receptors, Oxytocin; Receptors, Vasopressin; Reproduction; Sexual Behavior, Animal; Social Behavior; Species Specificity; Vasopressins
PubMed: 33580133
DOI: 10.1038/s41598-021-83342-6 -
International Journal of Molecular... Mar 2020Oxytocin (OT)/vasopressin (VP) signaling system is important to the regulation of metabolism, osmoregulation, social behaviours, learning, and memory, while the...
Oxytocin (OT)/vasopressin (VP) signaling system is important to the regulation of metabolism, osmoregulation, social behaviours, learning, and memory, while the regulatory mechanism on ovarian development is still unclear in invertebrates. In this study, ot/vp-like and its receptor (ot/vpr-like) were identified in the mud crab Scylla paramamosain. ot/vp-like transcripts were mainly expressed in the nervous tissues, midgut, gill, hepatopancreas, and ovary, while ot/vpr-like were widespread in various tissues including the hepatopancreas, ovary, and hemocytes. In situ hybridisation revealed that ot/vp-like mRNA was mainly detected in 6-9 clusters in the cerebral ganglion, and oocytes and follicular cells in the ovary, while ot/vpr-like was found to localise in F-cells in the hepatopancreas and oocytes in the ovary. In vitro experiment showed that the mRNA expression level of vg in the hepatopancreas, vgr in the ovary, and 17β-estradiol (E) content in culture medium were significantly declined with the administration of synthetic OT/VP-like peptide. Besides, after the injection of OT/VP-like peptide, it led to the significantly reduced expression of vg in the hepatopancreas and subduced E content in the haemolymph in the crabs. In brief, OT/VP signaling system might inhibit vitellogenesis through neuroendocrine and autocrine/paracrine modes, which may be realised by inhibiting the release of E.
Topics: Animals; Brachyura; Female; Ganglia, Invertebrate; Hepatopancreas; Ovary; Oxytocin; Receptors, Oxytocin; Receptors, Vasopressin; Transcriptome; Vasopressins; Vitellogenesis
PubMed: 32225106
DOI: 10.3390/ijms21072297 -
Scientific Reports Aug 2018The neurohormones arginine-vasopressin (AVP) and oxytocin (OT) synthesised in supraoptic and paraventricular nuclei of neurohypophysis regulate lactation, systemic water...
The neurohormones arginine-vasopressin (AVP) and oxytocin (OT) synthesised in supraoptic and paraventricular nuclei of neurohypophysis regulate lactation, systemic water homeostasis and nociception. Using transgenic rats expressing AVP and OT tagged with fluorescent proteins we demonstrate that both neurohormones are expressed in sensory neurones both in vitro, in primary cultures, and in situ, in the intact ganglia; this expression was further confirmed with immunocytochemistry. Both neurohormones were expressed in nociceptive neurones immunopositive to transient receptor potential vannilloid 1 (TRPV1) channel antibodies. The AVP and OT-expressing DRG neurones responded to AVP, OT, 50 mM K and capsaicin with [Ca] transients; responses to AVP and OT were specifically blocked by the antagonists of V AVP and OT receptors. Probing the extracellular incubation saline with ELISA revealed AVP and OT secretion from isolated DRGs; this secretion was inhibited by tetanus toxin (TeNT) indicating the role for vesicular release. Expression of OT, but not AVP in DRG neurones significantly increased during lactation. Together, the results indicate novel physiological roles (possibly related to nociception and mood regulation) of AVP and OT in the sensory neurones.
Topics: Animals; Dehydration; Exocytosis; Female; Fluorescence; Ganglia, Spinal; Lactation; Male; Nociception; Oxytocin; Pituitary Gland, Posterior; Rats, Transgenic; Receptors, Oxytocin; Receptors, Vasopressin; Sensory Receptor Cells; Vasopressins
PubMed: 30166555
DOI: 10.1038/s41598-018-31361-1