Administration Of Arginine Vasopressin Research Articles

Assessment of the hypothalamic-pituitary-adrenocortical axis function using a vasopressin stimulation test in neonatal foals.

Bacterial sepsis is the leading cause of death in foals and is associated with hypothalamic-pituitary-adrenocortical axis (HPAA) dysfunction. HPAA function can be evaluated by an arginine-vasopressin (AVP) stimulation test. Administration of AVP will stimulate a dose-dependent rise in systemic adrenocorticotropin-releasing hormone (ACTH) and cortisol in neonatal foals. There will be no response seen in corticotropin-releasing hormone (CRH) and baseline AVP will be within reference interval. Twelve neonatal foals, <72 hours old. HPAA function was assessed in foals utilizing 3 doses of AVP (2.5, 5, and 7.5 IU), administered between 24 and 48 hours of age in this randomized cross-over study. Cortisol, ACTH, CRH and AVP were measured at 0 (baseline), 15, 30, 60 and 90 minutes after AVP administration with immunoassays. The fold increase in cortisol and ACTH was calculated at 15 and 30 minutes compared to baseline. All doses of AVP resulted in a significant increase in cortisol concentration over time, and a dose-dependent increase in ACTH concentration over time. ACTH and cortisol were significantly increased at 15 and 30 minutes, respectively after all 3 doses of AVP compared to baseline (P < .01). There was no change in endogenous CRH after stimulation with AVP. Administration of AVP is safe and results in a significant rise in ACTH and cortisol in neonatal foals. A stimulation test with AVP (5 IU) can be considered for HPAA assessment in septic foals.

Central diabetes insipidus with anti-rabphilin-3A antibody positivity causing hypovolemic shock after resection of tumorous lesions in the pelvic cavity.

A 36-year-old female was pointed out to have liver enzyme elevation by routine health checkup. Subsequent contrast-enhanced CT scan identified gigantic uterine fibroids and retroperitoneal tumor. She was referred to the gynecologist at JA Toride Medical Center and planned to undergo a uterus enucleation and biopsy of the retroperitoneal tumor. The surgery was conducted without any troubles. After the surgery, the patient presented polyuria with urine volume 10-20 L a day and developed hypovolemic shock. Laboratory test revealed hypotonic urine and hypernatremia. Arginine vasopressin (AVP) loading test suggested shortage of endogenous vasopressin. Since the subcutaneous administration of AVP was not sufficient to control the urine volume, continuous intravenous infusion of AVP was initiated. After achieving hemodynamic stability, the treatment was switched to oral desmopressin. MRI finding indicated attenuation of high signal in posterior pituitary in T1 weighted image while neither enlargement of pituitary nor thickening of pituitary stalk was indicated by enhanced MRI. Hypertonic salt solution test indicated no responsive elevation of AVP, confirming the diagnosis of central diabetes insipidus (CDI). Her anterior pituitary function was preserved. Only anti-rabphilin-3A antibody was found positive in the serum of the patient, while other secondary causes for CDI were denied serologically and radiologically. Hence, lymphocytic infundibuloneurohypophysitis (LINH) was suspected as the final diagnosis. Hormonal replacement therapy by nasal desmopressin was continued and the patient managed to control her urine volume. In cases of CDI considered idiopathic with conventional examinations, anti-rabphilin-3A antibody may be a clue for determining the cause as LINH.

Abstract 057: Macula Densa Stimulation Acutely Increases Afferent Renal Nerve Activity And Blood Pressure

Macula densa (MD) cells in the kidney are known to regulate renal hemodynamics and the renin-angiotensin system, and indirectly systemic blood pressure (BP). However, neuron-like differentiation and activity as non-traditional MD functions are emerging. This study addressed the hypothesis that MD cells function similarly to peripheral ganglia, form neuronal networks that are part of the peripheral (renal) nervous system and synapse with renal afferent/efferent nerves as a new pathway for the direct control of sympathetic tone and BP. Single cell MD Ca 2+ signaling was analyzed in vivo using intravital multiphoton microscopy (MPM) of MD-G6 mice that selectively express the ratiometric Ca 2+ reporter GCaMP6f/tdTomato in MD cells. Afferent renal nerve activity (ARNA) was isolated and measured via recording electrodes. Systemic BP was monitored via the cannulated carotid artery. Optogenetic MD stimulation was induced by blue light (470nm) exposure of the whole left kidney of MD-Ai27 mice that selectively express the depolarizing channelrhodopsin ChR2 in MD cells. Pacemaker-like regular Ca 2+ oscillations (4-fold elevations in baseline Ca 2+ and frequency of 0.03 Hz) and their cell-to-cell propagation via long, axon-like processes were exclusively confined to the MD area. Bulk and scRNA seq and MD transcriptome analysis identified the high expression of genes related to synaptic transmission that was validated by immunohistochemistry. Acute intra-renal infusion of arginine-vasopressin (AVP) produced 3-fold increase in MD Ca 2+ firing frequency (via the MD-specific AVPR1a) and a dose-dependent increase in ARNA and BP (saline: -1±1; 0.01ug/mL: 2±1; 0.1ug/mL: 7±2; 0.25ug/mL: 7±3; 0.5ug/mL: 10±3; 1.0ug/mL: 23±13). IV administration of AVP (0.25ug/mL) did not significantly alter ARNA (108±3%, n=3) but produced a significant increase in arterial blood pressure (40±6mmHg, n=3). Blue light exposure of MD-Ai27 mouse kidneys acutely and reversibly increased systemic BP by 22±5mmHg (P&lt;0.05, n=5). In summary, MD cells send interoceptive signals to the brain via renal sensory afferent nerves to directly control BP. Targeting of novel MD mechanisms may result in exciting new therapeutic opportunities for renal and cardiovascular diseases and hypertension.

Dissociated modulations of intranasal vasopressin on prosocial learning between reward-seeking and punishment-avoidance.

As an integral ingredient of human sociality, prosocial behavior requires learning what acts can benefit or harm others. However, it remains unknown how individuals adjust prosocial learning to avoid punishment or to pursue reward. Given that arginine vasopressin (AVP) is a neuropeptide that has been involved in modulating various social behaviors in mammals, it could be a crucial neurochemical facilitator that supports prosocial learning. In 50 placebo controls and 54 participants with AVP administration, we examined the modulation of AVP on the prosocial learning characterized by reward and punishment framework, as well as its underlying neurocomputational mechanisms combining computational modeling, event-related potentials and oscillations. We found a self-bias that individuals learn to avoid punishment asymmetrically more severely than reward-seeking. Importantly, AVP increased behavioral performances and learning rates when making decisions to avoid losses for others and to obtain gains for self. These behavioral effects were underpinned by larger responses of stimulus-preceding negativity (SPN) to anticipation, as well as higher punishment-related feedback-related negativity (FRN) for prosocial learning and reward-related P300 for proself benefits, while FRN and P300 neural processes were integrated into theta (4-7 Hz) oscillation at the outcome evaluation stage. These results suggest that AVP context-dependently up-regulates altruism for concerning others' losses and reward-seeking for self-oriented benefits. Our findings provide insight into the selectively modulatory roles of AVP in prosocial behaviors depending on learning contexts between proself reward-seeking and prosocial punishment-avoidance.

Arginine Vasopressin is not elevated in Early Pregnancy Loss

BackgroundAdministration of arginine vasopressin (AVP) has been previously shown to influence myometrial contractility during the first trimester of pregnancy in women who were undergoing a planned therapeutic abortion. Consequently, it was hypothesized that AVP may play a role in early spontaneous pregnancy loss. AVP is made in a 1:1 molar ratio with copeptin; thus, copeptin can be used as a surrogate measure of AVP. While early pregnancy loss is likely a multifactorial problem, we sought to fill the gap in knowledge of the causes of using pre‐collected samples from pregnancies that subsequently underwent spontaneous abortion and matched controls.MethodsA retrospective case control study was performed using plasma samples from the Maternal Fetal Tissue Bank (IRB# 200910784) at the University of Iowa Hospitals &amp; Clinics. Whole blood samples were collected (ACD‐A tubes, Becton Dickinson) at confirmation of pregnancy appointments in which a viable pregnancy was detected by ultrasound (6‐10 weeks gestation). Samples were processed and plasma aliquots were snap frozen and stored at ‐80oC until analysis. Control samples (N=67) from viable, healthy pregnancies were matched by gestational age, race, ethnicity, and body mass index to cases (N=123). Copeptin was measured by an automated immunoassay (Brahms KRYPTOR) and total protein concentration via a bicinchoninic acid (BCA) protein assay (Pierce). Copeptin concentrations were normalized to total protein in samples. Continuous variables were analyzed by T test.ResultsNo significant differences were detected in plasma samples that were collected while the pregnancies appeared viable. Copeptin was 7.2 +/‐ 6.0 mg/dL in case plasma samples and 6.0 +/‐ 3.4 mg/dL in control plasma samples (P=0.066). It is unclear if vasopressin increases acutely prior to the occurrence of spontaneous abortion.ConclusionThese results suggest that vasopressin cannot be used to identify pregnancies at risk of early loss at the time of pregnancy confirmation.

Developmental exposure to intranasal vasopressin impacts adult prairie vole spatial memory

Spatial memory is critical for many tasks necessary for survival (i.e., locating mates and food resources). The two mammalian nonapeptides arginine vasopressin (AVP) and oxytocin (OT) are mechanistically important in modulating memory ability, albeit in contrasting ways. In general, AVP facilitates memory consolidation and retrieval while OT is an amnesic. Although AVP and OT are known to have these memory effects, past work has focused on their impact in social memory with little research on their effects on spatial memory. In this experiment, we tested the impact of AVP and OT on spatial memory as determined by performance in the Morris water maze (MWM). We administered doses of AVP, OT, or saline (a control) intranasally to male prairie voles (Microtus ochrogaster), a species whose spatial memory is hypothesized to impact their mating tactics. We also investigated if acute doses (given immediately prior to the memory trial in the MWM) and chronic doses (given daily during adolescence) had differing impacts on spatial cognition. We found that chronic intranasal administration of AVP during post-wean development improved spatial memory performance. In contrast, both chronic and acute administration of OT and acute administration of AVP had no impact on spatial memory. These results together suggest that 1) chronic exposure to AVP has organizational effects on spatial memory in the prairie vole, and 2) acute administration of nonapeptides does not impact the retrieval of spatial memories.

The Changes of Amygdala Transcriptome in Autism Rat Model After Arginine Vasopressin Treatment

BackgroundSome studies have shown that arginine vasopressin (AVP) can significantly improve the social interaction disorder of autism, but the mechanism remains unclear.MethodsFemale Wistar rats were intraperitoneally injected with VPA or normal saline at embryonic day 12.5 to establish an autism model or normal control in their offspring. Male offspring prenatally exposed to VPA were randomly assigned to two groups: the VPA-induced autism model group and the AVP group. The rats in the AVP group were treated with intranasal AVP at postnatal day (PND) 21 and for 3 weeks. The VPA-induced autism model group was given the same dose of normal saline in the same way. Behavioral responses were evaluated in the open field and three-chambered social test apparatus; the expression levels of AVP in serum were detected by enzyme-linked immunosorbent assay kit, and the gene expression levels on the amygdala were measured by RNA-seq at PND42.ResultsIntranasal administration of AVP can significantly improve the social interaction disorder and elevate the levels of AVP in serum. Transcriptome sequencing results showed that 518 differently expressed genes (DEGs) were identified in the VPA-induced autism model group compared with the control in this study. Gene Ontology biological process enrichment analysis of DEGs showed that the VPA-induced autism model group had significant nervous system developmental impairments compared with the normal group, particularly in gliogenesis, glial cell differentiation, and oligodendrocyte differentiation. Gene Set Enrichment Analysis (GSEA) enrichment analysis also showed that biological process of oligodendrocyte differentiation, axoneme assembly, and axon ensheathment were inhibited in the VPA-induced autism model group. Pathway enrichment analysis of DEGs between the control and VPA-induced autism model group showed that the PI3K/AKT and Wnt pathways were significantly dysregulated in the VPA-induced autism model group. Few DEGs were found when compared with the transcriptome between the VPA-induced autism model group and the AVP treatment group. GSEA enrichment analysis showed deficits in oligodendrocyte development and function were significantly improved after AVP treatment; the pathways were mainly enriched in the NOTCH, mitogen-activated protein kinase, and focal adhesion signaling pathways, but not in the PI3K/AKT and Wnt pathways. The expression patterns analysis also showed the same results.ConclusionAVP can significantly improve the social interaction disorder of VPA-induced autism model, and AVP may target behavioral symptoms in autism by modulating the vasopressin pathways, rather than primary disease mechanisms.

Betamethasone reverses AVP-induced dysfunction in trophoblast cells

Previously published data demonstrate that arginine vasopressin (AVP) secretion is elevated throughout gestation in pregnancies affected by preeclampsia. Additionally, chronic infusion of AVP in mice mimics human preeclampsia with pregnancy-specific hypertension, glomerular endotheliosis, proteinuria, and inflammation. In this AVP-infusion mouse model, betamethasone (BMTZ) has been shown to reverse the preeclampsia phenotype. Corticosteroids have previously been used to ameliorate human HELLP syndrome. Steroids have pleotropic therapeutic effects. The mechanism of BMTZ in reversing preeclampsia is unknown. The objective of this study is to determine if BMTZ improves AVP-induced placental dysfunction. Cell migration of HTR8/SVneo cells was analyzed via closure of a 500um gap over 48 hours (Ibidi). Cells were treated with saline, AVP + vasopressin receptor antagonists, and AVP + BMTZ. The area of migration was imaged and calculated (Olympus Cell Sens) and percent change from baseline area was calculated. MMP-9, a marker of inflammation, was measured in cultured media using a commercially available ELISA (Invitrogen). Statistical significance was determined by ANOVA (α=0.05). At 48 hours, AVP demonstrated lower cell migration in comparison to saline (23.8 vs. 32.3 percent change). This dysfunction was reversed with the addition BMTZ (53.8 vs. 32.3 percent change, p< 0.001). Administration of AVP + AVP antagonists (Conivaptan [29.4], Relcovaptan [32.5], Tolvaptan [35.4]) did not significantly affect migration (p >0.05). MMP-9 concentration was significantly lowered in the cell culture supernatant of cells treated with AVP+BMTZ vs. AVP alone (0.242 vs. 0.286 ng/mL, p=0.04). Treating HTR8/Svneo trophoblastic cells in vitro with AVP results in abnormal migration and cytokine expression. BMTZ reverses this AVP-induced dysfunction. In part, this effect may be due to a reversal of MMP-9 associated inflammation. Our results suggest that further investigation is warranted in the use of betamethasone as a novel therapeutic strategy for preeclampsia.

Effect of Constant Illumination on the Function of the Hypothalamic-Pituitary-Adrenal Axis in Nonhuman Primates.

We studied the effect of constant illumination on the effects of administration of arginine vasopressin (AVP), one of the most important regulators of the key adaptive hypothalamic-pituitary-adrenal (HPA) axis under basal conditions and during stress, as well as on the circadian rhythm of activity of HPA axis and the pineal gland in laboratory primates. In young adult female rhesus monkeys exposed to constant illumination for 7 weeks, the rise in the concentration of ACTH and cortisol in response to administration of AVP was markedly reduced in comparison with both the basal period and with the control group of animals. In addition, a destructive effect of constant lighting on circadian rhythm of cortisol secretion was observed in the absence of significant circadian changes in melatonin secretion. The inhibitory effect of constant illumination on the function of the HPA axis under basal conditions and under conditions of its activation can reduce the body's adaptive abilities.

Intranasal vasopressin modulates resting state brain activity across multiple neural systems: Evidence from a brain imaging machine learning study

Arginine vasopressin (AVP), a neuropeptide with widespread receptors in brain regions important for socioemotional processing, is critical in regulating various mammalian social behavior and emotion. Although a growing body of task-based brain imaging studies have revealed the effects of AVP on brain activity associated with emotion processing, social cognition and behaviors, the potential modulations of AVP on resting-state brain activity remain largely unknown. Here, the current study addressed this issue by adopting a machine learning approach to distinguish administration of AVP and placebo, employing the amplitude of low-frequency fluctuation (ALFF) as a measure of resting-state brain activity. The brain regions contributing to the classification were then subjected to functional connectivity and decoding analyses, allowing for a data-driven quantitative inference on psychophysiological functions. Our results indicated that ALFF across multiple neural systems were sufficient to distinguish between AVP and placebo at individual level, with the contributing regions distributed across the social cognition network, sensorimotor regions and emotional processing network. These findings suggest that the role of AVP in socioemotional functioning recruits multiple brain networks distributed across the whole brain rather than specific localized neural pathways. Beyond these findings, the current data-driven approach also opens a novel avenue to delineate neural underpinnings of various neuropeptides or hormones.

Morphofunctional Alterations of the Hypothalamus and Social Behavior in Autism Spectrum Disorders.

An accumulating body of evidence indicates a tight relationship between the endocrine system and abnormal social behavior. Two evolutionarily conserved hypothalamic peptides, oxytocin and arginine-vasopressin, because of their extensively documented function in supporting and regulating affiliative and socio-emotional responses, have attracted great interest for their critical implications for autism spectrum disorders (ASD). A large number of controlled trials demonstrated that exogenous oxytocin or arginine-vasopressin administration can mitigate social behavior impairment in ASD. Furthermore, there exists long-standing evidence of severe socioemotional dysfunctions after hypothalamic lesions in animals and humans. However, despite the major role of the hypothalamus for the synthesis and release of oxytocin and vasopressin, and the evident hypothalamic implication in affiliative behavior in animals and humans, a rather small number of neuroimaging studies showed an association between this region and socioemotional responses in ASD. This review aims to provide a critical synthesis of evidences linking alterations of the hypothalamus with impaired social cognition and behavior in ASD by integrating results of both anatomical and functional studies in individuals with ASD as well as in healthy carriers of oxytocin receptor (OXTR) genetic risk variant for ASD. Current findings, although limited, indicate that morphofunctional anomalies are implicated in the pathophysiology of ASD and call for further investigations aiming to elucidate anatomical and functional properties of hypothalamic nuclei underlying atypical socioemotional behavior in ASD.

AVP(4-8) Improves Cognitive Behaviors and Hippocampal Synaptic Plasticity in the APP/PS1 Mouse Model of Alzheimer's Disease.

Memory deficits with aging are related to the neurodegeneration in the brain, including a reduction in arginine vasopressin (AVP) in the brain of patients with Alzheimer's disease (AD). AVP(4-8), different from its precursor AVP, plays memory enhancement roles in the CNS without peripheral side-effects. However, it is not clear whether AVP(4-8) can improve cognitive behaviors and synaptic plasticity in the APP/PS1 mouse model of AD. Here, we investigated for the first time the neuroprotective effects of AVP(4-8) on memory behaviors and in vivo long-term potentiation (LTP) in APP/PS1-AD mice. The results showed that: (1) APP/PS1-AD mice had lower spontaneous alternation in the Y-maze than wild-type (WT) mice, and this was significantly reversed by AVP(4-8); (2) the prolonged escape latency of APP/PS1-AD mice in the Morris water maze was significantly decreased by AVP(4-8), and the decreased swimming time in target quadrant recovered significantly after AVP(4-8) treatment; (3) in vivo hippocampal LTP induced by high-frequency stimulation had a significant deficit in the AD mice, and this was partly rescued by AVP(4-8); (4) AVP(4-8) significantly up-regulated the expression levels of postsynaptic density 95 (PSD95) and nerve growth factor (NGF) in the hippocampus of AD mice. These results reveal the beneficial effects of AVP(4-8) in APP/PS1-AD mice, showing that the intranasal administration of AVP(4-8) effectively improved the working memory and long-term spatial memory of APP/PS1-AD mice, which may be associated with the elevation of PSD95 and NGF levels in the brain and the maintenance of hippocampal synaptic plasticity.

β-Arrestin 2 mediates arginine vasopressin-induced IL-6 induction via the ERK1/2-NF-κB signal pathway in murine hearts.

Evidence to date suggests that β-arrestins act beyond their role as adapter proteins. Arginine vasopressin (AVP) may be a factor in inflammation and fibrosis in the pathogenesis of heart failure. In the present study we investigated the effect of AVP on inflammatory cytokine IL-6 production in murine hearts and the impact of β-arrestin 2-dependent signaling on AVP-induced IL-6 production. We found that administration of AVP (0.5 U/kg, iv) markedly increased the levels of IL-6 mRNA in rat hearts with the maximum level occurred at 6 h. In β-arrestin 2 KO mouse hearts, deletion of β-arrestin 2 decreased AVP-induced IL-6 mRNA expression. We then performed in vitro experiments in adult rat cardiac fibroblasts (ARCFs). We found that AVP (10−9–10−6 M) dose-dependently increased the expression of IL-6 mRNA and protein, activation of NF-κB signaling and ERK1/2 phosphorylation, whereas knockdown of β-arrestin 2 blocked AVP-induced IL-6 increase, NF-κB activation and ERK1/2 phosphorylation. Pharmacological blockade of ERK1/2 using PD98059 diminished AVP-induced NF-κB activation and IL-6 production. The selective V1A receptor antagonist SR49059 effectively blocked AVP-induced NF-κB phosphorylation and activation as well as IL-6 expression in ARCFs. In AVP-treated mice, pre-injection of SR49059 (2 mg/kg, iv) abolished AVP-induced NF-κB activation and IL-6 production in hearts. The above results suggest that AVP induces IL-6 induction in murine hearts via the V1A receptor-mediated β-arrestin2/ERK1/2/NF-κB pathway, thus reveal a novel mechanism of myocardial inflammation in heart failure involving the V1A/β-arrestin 2/ERK1/2/NF-κB signaling pathway.

Effect of Low-Dose Supplementation of Arginine Vasopressin on Need for Blood Product Transfusions in Patients With Trauma and Hemorrhagic Shock

Current therapies for traumatic blood loss focus on hemorrhage control and blood volume replacement. Severe hemorrhagic shock, however, is associated with a state of arginine vasopressin (AVP) deficiency, and supplementation of this hormone may decrease the need for blood products in resuscitation. To determine whether low-dose supplementation of AVP in patients with trauma (hereinafter referred to as trauma patients) and with hemorrhagic shock decreases their need for transfused blood products during resuscitation. This randomized, double-blind placebo-controlled clinical trial included adult trauma patients (aged 18-65 years) who received at least 6 U of any blood product within 12 hours of injury at a single urban level 1 trauma center from May 1, 2013, through May 31, 2017. Exclusion criteria consisted of prehospital cardiopulmonary resuscitation, emergency department thoracotomy, corticosteroid use, chronic renal insufficiency, coronary artery disease, traumatic brain injury requiring any neurosurgical intervention, pregnancy, prisoner status, or AVP administration before enrollment. Data were analyzed from May 1, 2013, through May 31, 2017, using intention to treat and per protocol. After administration of an AVP bolus (4 U) or placebo, participants received AVP (≤0.04 U/min) or placebo for 48 hours to maintain a mean arterial blood pressure of at least 65 mm Hg. The primary outcome was total volume of blood product transfused. Secondary end points included total volume of crystalloid transfused, vasopressor requirements, secondary complications, and 30-day mortality. One hundred patients underwent randomization (49 to the AVP group and 51 to the placebo group). Patients were primarily young (median age, 27 years [interquartile range {IQR}, 22-25 years]) and male (n = 93) with penetrating trauma (n = 79). Cohort characteristics before randomization were well balanced. At 48 hours, patients who received AVP required significantly less blood products (median, 1.4 [IQR, 0.5-2.6] vs 2.9 [IQR, 1.1-4.8] L; P = .01) but did not differ in requirements for crystalloids (median, 9.9 [IQR, 7.9-13.0] vs 11.0 [8.9-15.0] L; P = .22) or vasopressors (median, 400 [IQR, 0-5900] vs 1400 [IQR, 200-7600] equivalent units; P = .22). Although the groups had similar rates of mortality (6 of 49 [12%] vs 6 of 51 [12%]; P = .94) and total complications (24 of 44 [55%] vs 30 of 47 [64%]; P = .37), the AVP group had less deep venous thrombosis (5 of 44 [11%] vs 16 of 47 [34%]; P = .02). Low-dose AVP during the resuscitation of trauma patients in hemorrhagic shock decreases blood product requirements. Additional research is necessary to determine whether including AVP improves morbidity or mortality. ClinicalTrials.gov identifier: NCT01611935.

Vasopressin receptors in islets enhance glucose tolerance, pancreatic beta-cell secretory function, proliferation and survival

Arginine vasopressin (AVP), a peptide secreted from the posterior pituitary, is chiefly regarded as a hormone involved in the regulation of body fluid balance and osmolality. However, recent evidence has revealed that posterior pituitary hormones can exert important actions on endocrine pancreatic function. In the present study, the presence of AVP receptors, namely Avpr1a (V1a), Avpr1b (V1b) and Avpr2 (V2) was demonstrated in murine islets as well as rodent BRIN BD11 and human 1.1B4 beta-cells. Further to this, AVP was shown to induce significant concentration-dependent (10−12 – 10−6 M) increases of insulin release from both rodent and human beta-cells, as well as mouse islets. Insulinotropic actions of AVP were completely annulled by specific V1a or V1b receptor antagonists, and partially abolished by an oxytocin receptor antagonist. In addition, beta-cell insulin secretory actions of AVP were augmented by both IBMX (200 μM) and KCl (30 mM) and linked to significantly increased cAMP production and [Ca2+]i. AVP substantially increased proliferation of rodent and human beta-cells. Moreover, AVP fully protected against cytokine-induced beta-cell apoptosis. AVP had no effect on glucagon secretion. Immunohistochemical examination of beta- and alpha-cells revealed co-expression of AVP with glucagon, and particularly insulin. Finally, administration of AVP in combination with glucose to mice significantly reduced blood glucose, which was associated with increased plasma insulin. These data indicate that AVP possesses novel and potentially important effects on pancreatic endocrine function. Understanding disturbances in islet AVP receptor signalling could reveal insight into the beta-cell defects associated with diabetes.

Oxytocin and vasopressin increase male-directed threats and vocalizations in female macaques

In a previous study, we reported that intranasal delivery of both oxytocin (OT) and arginine vasopressin (AVP) to male macaques relaxes spontaneous social interactions, flattens the existing dominance hierarchy, and increases behavioral synchrony with other monkeys. Here we report that intranasal OT and AVP administration modulates the behaviors of female macaque monkeys, but in robustly different ways from males. Most notably, both neuropeptides increase threatening and vocalization behaviors of females when they encounter males, and these behaviors effectively increase the social status of females over males. While OT and AVP heighten the confrontational nature of intersexual encounters, both peptides relax interactions between females. Finally, as previously reported for males, treating an individual female monkey with OT or AVP significantly modulates the behavior of her non-treated partner. Together, these findings show that OT and AVP can either inhibit or promote aggression, depending on sex and behavioral context, and call for a more careful, systematic examination of the functions of these neuropeptides in both sexes, especially in the context of therapeutics for human social disorders.

Effects of arginine vasopressin on Richardson's ground squirrel social and vocal behavior.

In nearly every vertebrate species examined thus far arginine vasopressin (AVP) and its homologues modulate behavior; thus, providing rich systems for comparative research. In rodents, AVP is best known for its modulation of social behavior; however, to date, research on AVPs effects on behavior have been limited to laboratory models and a few experiments using large outdoor enclosures. To extend our understanding of AVPs role in modulating social behavior and communication in an ecologically relevant context, we examined the effects of AVP on behavior of free-living Richardson's ground squirrels (Urocitellus richardsonii). To test the hypothesis that AVP influences social behavior and communication, we implanted osmotic minipumps into Richardson's ground squirrels and centrally administered AVP or saline as a control. Three different behavioral experiments quantifying behavior before and after AVP or saline administration were performed: a general behavior survey, a predator model presentation, and a social challenge test. AVP administration increased male vocalization rate when approached by a conspecific, but not when presented with a predator model. In males, social aggression decreased, but antipredator vigilance increased with AVP administration. Finally, AVP-treated females had increased "anxiety-like" behaviors during the social challenge test. Our data reveal that AVP has sex-specific effects on vocalizations and antipredator vigilance, as well as other social behaviors. Further, our data illustrate the importance of social context to AVPs modulation of behavior. (PsycINFO Database Record

Arginine vasopressin improves the memory deficits in Han Chinese patients with first-episode schizophrenia

The memory impairment is a core deficit in the first-episode schizophrenia patients. Arginine vasopressin (AVP) in the brain can improve learning and memory. We performed multicentre, randomized, double-blind, placebo-controlled, parallel-group clinical trial to study the cognitive functioning in Han Chinese first-episode schizophrenic patients in a 12-week treatment regime with the intranasal administration of AVP (128 cases) or placebo (131 cases) in addition to the conventional treatment. The methods of positive and negative syndrome scale (PANSS), Wechsler memory scale-4th edition (WMS-IV) and event-related potential (ERP) were used to study the effects of AVP on the cognitive function. The results showed that (1) AVP concentration decreased in cerebrospinal fluid (CSF) of the right-handed Han Chinese first-episode schizophrenic patients comparing with that of the health volunteers (7.1±1.5pg/ml vs 13.3±1.9pg/ml, p<0.01), and did not change in plasma; (2) AVP significantly improved PANSS scores including total scores, positive symptoms, negative symptoms and general psychopathology comparing with those of the placebo group; (3) AVP elevated WMS-IV scores including the long-term memory (accumulation), short-term memory (recognition, comprehension), immediate memory (number recitation) and memory quotient 4, 8 and 12 weeks after treatment; and (4) AVP did not influence the latency and wave amplitude of target stimulus of P300 of right-handed Han Chinese first-episode schizophrenic patients. The data suggested that AVP might improve cognitive process, such as memorizing and extraction of the information although there were many changes of cognitive functions in the right-handed Han Chinese first-episode schizophrenic patients.

Early Intranasal Vasopressin Administration Impairs Partner Preference in Adult Male Prairie Voles (Microtus ochrogaster).

Research supports a modulatory role for arginine vasopressin (AVP) in the expression of socially motivated behaviors in mammals. The acute effects of AVP administration are demonstrably pro-social across species, providing the justification for an ever-increasing measure of clinical interest over the last decade. Combining these results with non-invasive intranasal delivery results in an attractive system for offering intranasal AVP (IN-AVP) as a therapeutic for the social impairments of children with autism spectrum disorder. But, very little is known about the long-term effects of IN-AVP during early development. In this experiment, we explored whether a single week of early juvenile administration of IN-AVP (low = 0.05 IU/kg, medium = 0.5 IU/kg, high = 5.0 IU/kg) could impact behavior across life in prairie voles. We found increases in fecal boli production during open field and novel object recognition testing for the medium dose in both males and females. Medium-dose females also had significantly more play bouts than control when exposed to novel conspecifics during the juvenile period. Following sexual maturity, the medium and high doses of IN-AVP blocked partner preference formation in males, while no such impairment was found for any of the experimental groups in females. Finally, the high-dose selectively increased adult male aggression with novel conspecifics, but only after extended cohabitation with a mate. Our findings confirm that a single week of early IN-AVP treatment can have organizational effects on behavior across life in prairie voles. Specifically, the impairments in pair-bonding behavior experienced by male prairie voles should raise caution when the prosocial effects of acute IN-AVP demonstrated in other studies are extrapolated to long-term treatment.

Sex-specific effect of intranasal vasopressin, but not oxytocin, on emotional recognition and perception in schizophrenia patients

BackgroundImpairments in social behavior and cognition, such as the ability to identify others’ emotional state, are important features in schizophrenia. Arginine vasopressin (AVP) and oxytocin (OXT) and are nonapeptides that influence social cognition and behavior. Previous studies have shown that the administration of intranasal AVP or OXT may affect the ability to recognize facial emotions. The primary objective of this study was to investigate the effects of a single dose of AVP or OXT on social cognition in patients with schizophrenia. The secondary objective of the study was to test for sex-specific effects of intranasal AVP and OXT administration on social cognition.MethodsIn this double-blind, placebo-control, cross-over study, 34 patients diagnosed with schizophrenia or schizo-affective disorder, received a dose of AVP, OXT or placebo in three separate meetings. Forty-five minutes after administration, subjects performed facial emotion recognition tasks.ResultsThere were no significant main effects of hormone administration on the ability to recognize facial emotions between treatment conditions. However, AVP administration resulted in sex-specific differences in emotion recognition. Specifically, in men, AVP administration reduced the ability to recognize angry faces. In women, AVP administration reduced the ability to recognize sad faces and improved the ability to recognize fearful faces.ConclusionsThese findings indicate that intranasal AVP may affect the recognition of facial emotions differently in men and women. Thus, AVP may increase the differences between men and women on social cognition.Disclosure of interestThe authors have not supplied their declaration of competing interest.