Intranasal Arginine Vasopressin Research Articles

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.

Intranasal vasopressin expedites dishonesty in women

As an integral ingredient of human sociality, dishonesty can be both egocentric and altruistic, as well as gradually escalate. Here, we examined the influence of arginine vasopressin (AVP), a neuropeptide associated with human prosocial behaviors, on dishonest behaviors in men and women. In this double-blind and placebo-controlled study, 101 participants were randomized to administration of either 20 IU intranasal AVP or placebo. We used a two-party task to manipulate the incentive structure of dishonesty in the way of self-/other-serving repeatedly. For lies that benefit both themselves and others, women receiving intranasal AVP lied more than women receiving intranasal placebo and men receiving intranasal AVP. The dishonest behavior of women treated with AVP gradually escalated with repetition over time. These results suggest that AVP selectively regulates the escalation of dishonesty in women, contingent on the motivation of dishonesty. Our findings provide insight into gender-specific modulations of AVP on human dishonest behavior.

Vasopressin enhances human preemptive strike in both males and females

The neuropeptide arginine vasopressin (AVP), which is known to modulate a wide range of social behaviors in animals, has been identified as a modulator of various negative responses to social stimuli in humans. However, behavioral evidence directly supporting its involvement in human defensive aggression has been rare. We investigated the effect of intranasal AVP on defensive aggression in a laboratory experiment, using an incentivized economic game called the “preemptive strike game” (PSG). Participants played PSG individually (1 on 1) as well as in pairs (2 on 2) under either AVP or saline. We observed that exogenous but not basal AVP modulated the attack rate in PSG for both male and female participants. A model-based analysis of the aggregation of individual attack preferences into pair decisions revealed that the AVP effect on defensive aggression occurred mainly at the individual level and was not amplified at the pair level. Overall, these results present the first evidence that intranasal AVP promotes human defensive aggression for both males and females in a bilateral situation where each party can potentially damage the resources of the other party. These findings also parallel accumulating evidence from non-human animals concerning AVP’s involvement in territorial defense against potential intruders.

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.

Intranasal Vasopressin Relieves Orthopedic Pain After Surgery

BackgroundOrthopedic pain after surgery is very common and difficult to manage. Although intranasal arginine vasopressin (AVP) relieves headache (tension-type headache and migraine mostly), the effect of intranasal AVP on the orthopedic pain after surgery is unknown. AimsThis study investigated the effect of intranasal AVP on orthopedic pain after surgery in a randomized controlled trial with a double-blind design. ParticipantsThe study included 653 orthopedic patients and 661 health volunteers. MethodsOrthopedic pain was analyzed by the visual analogue scales (VAS) and AVP concentration was determined by radioimmunoassay. Results(1) intranasal AVP decreased the VAS level in orthopedic patients 2-4 weeks after surgery in a dose-dependent manner; (2) the cerebrospinal fluid (CSF) AVP concentration in orthopedic patients after surgery was higher than that in the health volunteers (38.57 ± 6.11 pg/mL vs 11.74 ± 2.85 pg/mL, p < .01), but had no change in plasma (p > .05); (3) CSF AVP concentration increased significantly in orthopedic patients during 24 hours after the intranasal AVP (p < .05 or .01), which related with VAS level negatively (all p < .01); (4) during 24 hours, intranasal AVP did not influence not only plasma AVP concentration, but also blood pressure, heart rate, respiratory rate and body temperature in orthopedic patients. CouclusionsThe findings contribute valuable information that intranasal AVP can treat orthopedic pain after surgery, and AVP could be an option for pain relief by intranasal administration.

Arginine Vasopressin Effects on Subjective Judgments and Neural Responses to Same and Other-Sex Faces in Men and Women

Arginine vasopressin (AVP) influences social and emotional behaviors across a wide range of species. In humans, intranasal AVP has been previously shown to alter physiological responses to and subjective judgments of same-sex faces in both men and women. The present study attempted to elucidate the neural mechanism for these effects by randomizing 40 healthy men and 40 healthy women to treatment with either 40 IU intranasal AVP or a saline placebo approximately 30 min before imaging their brain function with fMRI as they viewed same and other-sex faces. All subjects were also scanned a second time several days later with no treatment to evaluate the persistence of AVP effects over time. AVP acutely increased positive ratings of same-sex faces in women, with some evidence that these effects persisted until the second scan. While AVP had no acute effects on same-sex ratings in men, AVP increased positive ratings of same-sex faces several days later. On the other hand, AVP had no effect on other-sex face judgments in either sex. AVP modulation of brain function was focused on the nucleus accumbens (NAc) and the lateral septum, two reward processing areas involved in the formation of social bonds. AVP provoked acute increases in right NAc and bilateral lateral septum responses to female faces among men, with left lateral septum responses persisting over time while right NAc responses reversed over time. Finally, AVP modulated hypothalamic activation to faces in both men and women. The present study therefore indicates that intranasal AVP affects subjective ratings and neural responses to same and other-sex faces in men and women, with some effects persisting and others emerging over time. Future studies should investigate whether AVP effects are modulated by individual variables such as genotype, personality, or attachment style as previously reported for other nonapeptides.

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.

Oxytocin and vasopressin enhance responsiveness to infant stimuli in adult marmosets

The neuropeptides oxytocin (OT) and arginine-vasopressin (AVP) have been implicated in modulating sex-specific responses to offspring in a variety of uniparental and biparental rodent species. Despite the large body of research in rodents, the effects of these hormones in biparental primates are less understood. Marmoset monkeys (Callithrix jacchus) belong to a clade of primates with a high incidence of biparental care and also synthesize a structurally distinct variant of OT (proline instead of leucine at the 8th amino acid position; Pro8-OT). We examined the roles of the OT and AVP systems in the control of responses to infant stimuli in marmoset monkeys. We administered neuropeptide receptor agonists and antagonists to male and female marmosets, and then exposed them to visual and auditory infant-related and control stimuli. Intranasal Pro8-OT decreased latencies to respond to infant stimuli in males, and intranasal AVP decreased latencies to respond to infant stimuli in females. Our study is the first to demonstrate that Pro8-OT and AVP alter responsiveness to infant stimuli in a biparental New World monkey. Across species, the effects of OT and AVP on parental behavior appear to vary by species-typical caregiving responsibilities in males and females.

Effect of intranasal arginine vasopressin on human headache

Arginine vasopressin (AVP), a nonapeptide hormone of posterior pituitary, reaches the central nervous system from systemic blood circulation with a difficulty because of the blood–brain barrier (BBB). The interest has been expressed in the use of the nasal route for delivery of AVP to the brain directly, exploiting the olfactory pathway. Our previous study has demonstrated that AVP in the brain rather than the spinal cord and blood circulation plays an important role in rat pain modulation. For understanding the role of AVP on pain modulation in human, the communication tried to investigate the effect of intranasal AVP on human headache. The results showed that (1) AVP concentration in both plasma and cerebrospinal fluid (CSF) increased significantly in headache patients, who related with the headache level; (2) there was a positive relationship between plasma and CSF AVP concentration in headache patients; and (3) intranasal AVP could relieve the human headache in a dose-dependent manner. The data suggested that intranasal AVP, which was delivered to the brain through olfactory region, could treat human headache and AVP might be a potential drug of pain relief by intranasal administration.

The influence of light–dark rhythm to social development and the critical period in marmosets

The neuropeptides oxytocin (OT) and arginine-vasopressin (AVP) have been implicated in modulating sex-specific responses to offspring in a variety of uniparental and biparental rodent species. Despite the large body of research in rodents, the effects of these hormones in biparental primates are less understood. Marmoset monkeys (Callithrix jacchus) belong to a clade of primates with a high incidence of biparental care and also synthesize a structurally distinct variant of OT (proline instead of leucine at the 8th amino acid position; Pro8-OT). We examined the roles of the OT and AVP systems in the control of responses to infant stimuli in marmoset monkeys. We administered neuropeptide receptor agonists and antagonists to male and female marmosets, and then exposed them to visual and auditory infant-related and control stimuli. Intranasal Pro8-OT decreased latencies to respond to infant stimuli in males, and intranasal AVP decreased latencies to respond to infant stimuli in females. Our study is the first to demonstrate that Pro8-OT and AVP alter responsiveness to infant stimuli in a biparental New World monkey. Across species, the effects of OT and AVP on parental behavior appear to vary by species-typical caregiving responsibilities in males and females.

Intranasal vasopressin affects pair bonding and peripheral gene expression in male Callicebus cupreus

Arginine vasopressin (AVP) is a neuropeptide hormone and neurotransmitter that has peripheral functions in water regulation, and central functions in the stress response and social bonding in male rodents. In this study, we investigated the role of AVP in partner preference behavior in a monogamous primate, the coppery titi monkey (Callicebus cupreus). Seven titi males each received three intranasal treatments: saline, low AVP (40 IU) and high AVP (80 IU) in random order, 1 week apart. They experienced a series of stimulus exposures to their female partner, a female stranger and an empty cage. Males were more likely to contact the stimulus and do so faster when either female stimulus was present. When pretreated with saline, males contacted the stranger more frequently than their partner; when pretreated with the high dosage of AVP, males contacted their partner more frequently than the stranger. We used microarray to measure peripheral changes in gene expression associated with intranasal AVP and found reduced expression of several genes coding for proinflammatory cytokines. The data presented here suggest that intranasally administered AVP has both central influences on social behavior and peripheral influences on inflammation in a nonhuman primate.

Sex-specific influences of vasopressin on human social communication.

Arginine vasopressin (AVP) and related peptides affect social behaviors in numerous species, but AVP influences on human social functions have not yet been established. Here, we describe how intranasal AVP administration differentially affects social communication in men and women, and we propose a mechanism through which it may exert those influences. In men, AVP stimulates agonistic facial motor patterns in response to the faces of unfamiliar men and decreases perceptions of the friendliness of those faces. In contrast, in women, AVP stimulates affiliative facial motor patterns in response to the faces of unfamiliar women and increases perceptions of the friendliness of those faces. AVP also affected autonomic responsiveness to threatening faces and increased anxiety, which may underlie both communication patterns by promoting different social strategies in stressful contexts in men and women.

The effects of vasopressin on human facial responses related to social communication

Arginine vasopressin (AVP) and arginine vasotocin (AVT) influence social behaviors in a number of species from diverse taxonomic groups, therefore suggesting a conservation of social functions for these homologous neuropeptides during vertebrate evolution. However, whether or not AVP has the ability to directly influence social behavior in humans has not yet been determined. Because influences of AVT/AVP on behaviors related to social communication, particularly in aggressive contexts, are among the most consistently observed across species from diverse vertebrate groups, the present study was designed to determine if AVP administration would influence cognitive, autonomic and/or somatic responses to species-specific social stimuli important for agonistic communication in humans. Specifically, we tested the effects of intranasal AVP administration on attention towards emotionally expressive facial expressions, as well as on heart rate (HR), skin conductance (SC) and corrugator supercilii electromyograms (corrugator EMG) in response to these social stimuli. AVP did not affect attention toward, nor autonomic arousal in response to, emotionally neutral, happy or angry facial expressions, but it did selectively enhance the corrugator EMG responses evoked by emotionally neutral facial expressions, making them similar in magnitude to responses evoked by angry facial expressions in control subjects. Because this muscle group is involved in agonistic communication, these results suggest that AVP may influence aggression in human males by biasing individuals to respond to emotionally ambiguous social stimuli as if they were threatening/aggressive.