Exogenous Arginine Vasotocin Research Articles

Signaler’s Vasotocin Alters the Relationship between the Responder’s Forebrain Catecholamines and Communication Behavior in Lizards (Anolis carolinensis)

Dynamic fluctuations in the distribution of catecholamines across the brain modulate the responsiveness of vertebrates to social stimuli. Previous work demonstrates that green anoles (Anolis carolinensis) increase chemosensory behavior in response to males treated with exogenous arginine vasotocin (AVT), but the neurochemical mechanisms underlying this behavioral shift remains unclear. Since central catecholamine systems, including dopamine, rapidly activate in response to social stimuli, we tested whether exogenous AVT in signalers (stimulus animals) impacts catecholamine concentrations in the forebrain (where olfactory and visual information are integrated and processed) of untreated lizard responders. We also tested whether AVT influences the relationship between forebrain catecholamine concentrations and communication behavior in untreated receivers. We measured global catecholamine (dopamine = DA, epinephrine = Epi, and norepinephrine = NE) concentrations in the forebrain of untreated responders using high-performance liquid chromatography-mass spectrometry following either a 30-min social interaction with a stimulus male or a period of social isolation. Stimulus males were injected with exogenous AVT or vehicle saline (SAL). We found that global DA, but not Epi or NE, concentrations were elevated in lizards responding to SAL-males relative to isolated lizards. Lizards interacting with AVT-males had DA, Epi and NE concentrations that were not significantly different from SAL or isolated groups. For behavior, we found a significant effect of social treatment (AVT vs. SAL) on the relationships between (1) DA concentrations and the motivation to perform a chemical display (latency to tongue flick) and (2) Epi concentrations and time spent displaying mostly green body coloration. We also found a significant negative correlation between DA concentrations and the latency to perform a visual display but found no effect of social treatment on this relationship. These data suggest that catecholamine concentrations in the forebrain of untreated responders are associated with chemical and visual communication in lizards and that signaler AVT alters this relationship for some, but not all, aspects of social communication.

Arginine vasotocin affects vocal behavior but not selective responses to conspecific calls in male túngara frogs

Arginine vasotocin (AVT) and its homolog arginine vasopressin (AVP) modulate social behavior, including social communication. In anuran amphibians, male-male competition and female mate choice rely heavily on acoustic signaling. Behavioral experiments show that AVT influences motivation to call and vocal production. It may also influence how males process and respond to socially relevant auditory stimuli, but few studies have explored this possibility in this taxon. Túngara frogs produce a “whine” that is used for species recognition; in competition with other males they append one or more attractive “chucks” to the whine. Frequency modulation in the whine is an important cue for recognizing conspecifics, and gating of conspecific signals begins in the auditory midbrain. We used dynamic playback experiments to investigate the effects of exogenous AVT on males' responses to stimuli with species-typical and altered frequency modulation. We used avoidance of call overlap as evidence that a male recognizes a stimulus as salient and the production of attractive chucks as evidence of his competitive response to a proximate rival. We used call rate, whine duration, and whine frequency as measures of motivation and motor production. Males responded selectively to a stimulus with species-typical frequency modulation. Following treatment with AVT, they increased call rate and altered whines and chucks in a way that suggests increased air flow during the whine. We did not, however, find evidence that treatment with AVT alters the salience of frequency modulation in recognizing and responding to acoustic signals, at least for the stimuli used in this study.

Arginine vasotocin impacts chemosensory behavior during social interactions of Anolis carolinensis lizards

In reptiles, arginine vasotocin (AVT) impacts the performance of and response to visual social signals, but whether AVT also operates within the chemosensory system as arginine vasopressin (AVP) does in mammals is unknown, despite social odors being potent modifiers of competitive and appetitive behavior in reptiles. Here, we ask whether elevated levels of exogenous AVT impact rates of chemical display behavior (e.g. tongue flicks) in adult males, and whether conspecific males or females can chemically discriminate between competitor males based on differing levels of exogenous AVT in green anoles (Anolis carolinensis). We injected wild-caught green anole males with either AVT (AVT-Males) or a vehicle control (CON-Males) solution, then presented treated males with a conspecific stimulus (Intruder-Male or Intruder-Female) and filmed 30-minute interactions. We found that AVT-Males were faster than CON-Males to perform a tongue flick to conspecifics, and faster to chemically display toward Intruder-Females, suggesting AVT increased male interest in available chemical information during social encounters. Intruders performed more lip smack behavior when interacting with AVT-Males than with CON-Males, and Intruder-Males performed more tongue flick behavior when interacting with AVT-Males than with CON-Males, suggesting anoles can discriminate between conspecifics based on exogenous AVT levels. We also found a reduction in Intruder movement behavior when Intruders were paired with AVT-Males. This study provides empirical support for AVT-mediated chemosensory behavior in reptilian social interactions, in a microsmatic lizard species, suggesting the mechanism by which mammalian AVP and non-mammalian AVT mediate chemosensory behavior during social interactions may be evolutionarily conserved.

Arginine vasotocin regulates social ascent in the African cichlid fish Astatotilapia burtoni

Neuropeptides modulate many aspects of behavior and physiology in a broad range of animals. Arginine vasotocin (AVT) is implicated in mediating social behavior in teleost fish, although its specific role varies between species, sexes, life stages, and social context. To investigate whether the effects of AVT on behavior depend on social context, we used the African cichlid fish Astatotilapia burtoni, which is well-known for its remarkable behavioral plasticity. We pharmacologically manipulated the AVT system in established socially dominant and subordinate A. burtoni males, as well as in males ascending to dominance status in a socially unstable environment. Our results show that exogenous AVT causes a stress response, as evidenced by reduced behavioral activity and increased circulating levels of cortisol in established dominant and subordinate males. Administration of the AVT antagonist Manning compound, on the other hand, did not affect established subordinate or dominant males. However, AVT antagonist-treated males ascending from subordinate to dominant status exhibited reduced aggressive and increased courtship behavior compared to vehicle-treated animals. Finally, we measured circulating cortisol levels and brain gene expression levels of AVT and its behaviorally relevant V1a2 receptor in all three social phenotypes and found that plasma cortisol and mRNA levels of both genes were increased in ascending males compared to dominant and subordinate males. Our results provide a more detailed understanding of the role of the AVT system in the regulation of complex behavior in a dynamically changing social environment.

Arginine vasotocin activates aggressive calls during paternal care in the Puerto Rican coquí frog, Eleutherodactylus coqui

The Puerto Rican coquí frog, Eleutherodactylus coqui, is a directly developing frog that exhibits male territoriality and paternal behaviors. Male frogs also produce advertisement and aggressive vocalizations or calls. Territorial males emit advertisement calls to delineate territories and attract mates. Paternal males guard and brood the directly developing embryos during embryogenesis and up to five days after hatching; advertisement calling is normally absent or infrequent during paternal care. Territorial and paternal males commonly produce aggressive calls during agonistic situations. The neuropeptide, arginine vasotocin (AVT), has been shown to promote calling in anurans, including E. coqui. The objective of this study was to determine if exogenous AVT promotes calling and territorial behavior in paternal males and if it promotes males to abandon their offspring. Injections (IP) of AVT were given to paternal males immediately before the scotoperiod. Frogs were monitored for at least four hours after the injection and the following morning for calling activity and abandonment of egg clutches. AVT-injected males showed a dramatic and significant increase in aggressive calls compared to control males (saline injections). Exogenous AVT did induce advertisement calling in some paternal males but did not significantly elevate paternal males to territorial status nor did it significantly induce abandonment of eggs/embryos. In conclusion, the type of vocalization that AVT activates in E. coqui depends upon the reproductive state of the male and the social environment that surrounds the male.

Individual Behavioral and Neuronal Phenotypes for Arginine Vasotocin Mediated Courtship and Aggression in a Territorial Teleost

The neuropeptide arginine vasotocin (AVT) is well known to modulate both aggression and affiliation, yet few studies relate individual behavioral state to a quantitative assessment of AVT distribution in the brain. Here, using a wild population of beaugregory damselfish, Stegastes leucostictus, we assess: (1) the effect of AVT on courtship, and (2) with reference to our previous study on AVT modulation of aggression in this species, the relationship between AVT-like immunoreactive (ir) fiber distribution in the forebrain’s preoptic area and individual courtship and aggression levels. Exogenous AVT did not affect courtship, yet Manning compound, an arginine vasopressin (AVP) V1a receptor antagonist, significantly lowered but did not eradicate courtship. Consistent with AVT’s known facilitation of aggression in this species, the density of AVT-ir fibers in the preoptic area was significantly negatively correlated to aggression. Our findings match similar behavioral and immunoreactive patterns of neuropeptide secretion in other taxa. Unlike aggression, preoptic AVT-ir fiber density was not significantly correlated to individual courtship levels. The results suggest a differential involvement of preoptic AVT neurons and/or their receptors in supporting the expression of aggression and courtship.

Treatment with arginine vasotocin alters mating calls and decreases call attractiveness in male túngara frogs

The peptide hormone arginine vasotocin (AVT) and its mammalian homolog arginine vasopressin modulate a variety of social behaviors in vertebrates. In anurans, AVT influences the production of advertisement calls, the acoustic signals that males use to attract females and repel rival males. In this study, we investigate the effects of AVT on call characteristics in the túngara frog ( Physalaemus pustulosus). Túngara frogs produce a “whine” that is important for species recognition; they may also produce a second, attractive call component, the “chuck”. We used a field playback experiment to determine changes in male calling behavior following treatment with AVT. A previous study showed that AVT alters call rate and the production of chucks; in the current analysis, we focus on changes in the whine. Males produce shorter whines with higher initial frequencies following treatment with AVT. Call changes do not vary with a social stimulus. We also used female phonotaxis experiments to investigate the effects of call changes on female mate choice. Females disfavor the calls produced by males treated with exogenous AVT. We suggest that AVT influences motivation to call and the motor control of call production, but that over-stimulation of the vocal system limited the production of attractive calls in this experimental context.

Seasonal changes in hypothalamic-pituitary-adrenal axis sensitivity in free-living house sparrows ( Passer domesticus)

Recent evidence indicates that house sparrows ( Passer domesticus) seasonally regulate corticosterone responses to capture, handling, and restraint. Responses during molt and in the fall are lower than responses in the winter and while breeding. This study tested whether changes in either adrenal tissue responsiveness to adrenocorticotropin (ACTH) or pituitary responsiveness to corticotropin releasing factor (CRF) or arginine vasotocin (AVT) could provide the mechanism regulating these seasonal changes. House sparrows were captured at two sites (Massachusetts and New Mexico, USA) and during the above four seasons and injected with exogenous ACTH, CRF, and AVT. ACTH stimulated further corticosterone release in all birds except Massachusetts birds in the winter, suggesting that reduced adrenal sensitivity to ACTH cannot explain reduced corticosterone release during fall and molt. However, exogenous ACTH was less effective during molt at both sites, implying that adrenal sensitivity does change. Pituitary sensitivity also changed seasonally, but these pituitary changes did not match the seasonal changes in corticosterone release. CRF and AVT only succeeded in elevating corticosterone in the spring in Massachusetts birds and in the winter in New Mexico birds, whereas CRF alone also stimulated corticosterone release in New Mexico birds in the fall. Taken together, these data indicate that house sparrows can alter the amount of corticosterone released from adrenal tissue, the amount of ACTH released from the pituitary, and the amount of CRF and AVT released from the hypothalamus, but that none of these changes correlate with seasonal changes in corticosterone release. Consequently, seasonal modulation of corticosterone release in house sparrows appear to result from a complicated mix of adrenal, pituitary, and hypothalamic changes that also vary seasonally.

Effects of arginine vasotocin (AVT) on the behavioral, cardiovascular, and corticosterone responses of starlings ( Sturnus vulgaris) to crowding

Previous studies in European starlings have concluded that conspecific crowding can be a significant stressor that is capable of simultaneously altering behavior, heart rate, and corticosterone (CORT) concentrations. It was hypothesized that the peptide hormone arginine vasotocin (AVT) has a role in the regulation of these three types of responses to crowding. Four male and four female resident starlings were submitted to nine combinations of 3 crowding treatments (0, 1, or 5 intruder starlings) and 3 subcutaneous injections (1, 4 μg AVT, and saline control). Resident starlings were given a treatment injection, their heart rate and behavior were monitored for 30 min, 0, 1, or 5 intruder Starlings were allowed to enter the residents cage, and HR and behavior were monitored for another 30 min. Blood samples were taken before and after all treatments to assess CORT concentrations. Exogenous AVT decreased the frequency of maintenance behaviors (feeding, drinking, preening, and beak wiping), as well as activity in resident starlings. Although aggressive behaviors upright posture, head feather expansion, and pecking) increased during crowding, these increases were significantly attenuated by AVT. Heart rate was significantly lower during these behavioral effects, and the CORT data indicate that the cardiovascular and behavioral effects are not dependent on significant increases in CORT. These data support the hypothesis that AVT's attenuation of general behavior and crowding induced aggression are modulated by a cardiovascular mechanism.

Exogenous vasotocin alters aggression during agonistic exchanges in male Amargosa River pupfish ( Cyprinodon nevadensis amargosae)

Pupfishes in the Death Valley region have rapidly differentiated in social behaviors since their isolation in a series of desert streams, springs, and marshes less than 20,000 years ago. These habitats can show dramatic fluctuations in ecological conditions, and pupfish must cope with the changes by plastic physiological and behavioral responses. Recently, we showed differences among some Death Valley populations in brain expression of arginine vasotocin (AVT). As AVT regulates both hydromineral balance and social behaviors in other taxa, these population differences may indicate adaptive changes in osmoregulatory and/or behavioral processes. To test whether AVT is relevant for behavioral shifts in these fish, here we examined how manipulations to the AVT system affect agonistic and reproductive behaviors in Amargosa River pupfish ( Cyprinodon nevadensis amargosae). We administered exogenous AVT (0.1, 1, and 10 μg/g body weight) and an AVP V 1 receptor antagonist (Manning compound, 2.5 μg/g body weight) intraperitoneally to males in mixed-sex groups in the laboratory. We found that AVT reduced the initiation of aggressive social interactions with other pupfish but had no effect on courtship. The effects of AVT were confirmed in males in the wild where AVT (1 μg/g body weight) reduced the aggressive initiation of social interactions and decreased aggressive responses to the behavior of other males. Combined, these results show that AVT can modulate agonistic behaviors in male pupfish and support the idea that variation in AVT activity may underlie differences in aggression among Death Valley populations.

Regulation of the hypothalamic-pituitary-adrenal axis in free-living pigeons.

We studied feral free-living pigeons (Columba livia) to determine whether either unstressed or stress-induced corticosterone release was altered during a prebasic molt. The pigeons were at various stages of molt throughout the study, but corticosterone responses in molting and nonmolting birds did not differ. This was further reflected in equivalent adrenal responses to exogenous adrenocorticotropic hormone (ACTH), suggesting equivalent steroidogenic capacity of adrenal tissues during both physiological states. There was a slight change, however, in pituitary regulation during molt. Whereas exogenous arginine vasotocin (AVT) elevated corticosterone levels in nonmolting birds, during molt an equivalent dose of AVT was ineffective, suggesting that the pituitary is less sensitive to an AVT signal during molt. AVT also appears to be more effective than corticotropin-releasing factor at eliciting ACTH release in pigeons. Overall, these data indicate that pigeons regulate their corticosterone release differently during molt than other avian species studied to date.

Effects of arginine vasotocin, isotocin and melatonin on blood pressure in the conscious atlantic cod (Gadus morhua): hormonal interactions?

The effects of exogenous arginine vasotocin (AVT), isotocin (IT) and melatonin on the blood pressure of conscious Atlantic cod (Gadus morhua) were examined. Ventral aortic blood pressure (PVA) was recorded from a cannula inserted into the afferent branchial artery of the third gill arch. Dorsal aortic blood pressure (PDA) was recorded via a cannula implanted into the efferent branchial artery in the same gill arch. Each fish received two doses (10 and 50 ng kg-1) of AVT, IT and melatonin. AVT was also administered in combination with melatonin. Injection of 10 ng kg-1 AVT produced significant hypertension, especially in animals injected during the daytime. In contrast, the same dose of IT induced no significant change in either PVA or PDA. Administration of 10 ng kg-1 melatonin at night caused a long-lasting decrease in both parameters. Melatonin also inhibited the increase in blood pressure elicited by AVT. These results indicate that AVT, but not IT, is vasopressor in the cod. The effects of combined administration of melatonin and AVT show the antihypertensive action of melatonin in AVT-induced hypertension.

Seasonal Changes in Adrenal Sensitivity Alter Corticosterone Levels in Gambel's White-Crowned Sparrows ( Zonotrichia leucophrys gambelii)

Recent work indicates that Gambel's white-crowned sparrows modulate corticosterone release seasonally in response to capture and restraint. Free-living white-crowned sparrows dramatically elevate both baseline and stress-induced corticosterone levels during the breeding season compared with either wintering or migrating birds. Although corticosteroid binding globulin capacity also rises during breeding, it does not fully compensate for elevated glucocorticoid levels. Consequently, we examined what hypothalamic-pituitary-adrenal axis changes could account for seasonal changes in glucocorticoid levels. During winter and fall migration, exogenous ACTH failed to elevate corticosterone levels beyond the response to capture and handling, suggesting that the adrenal's ability to release corticosterone limits circulating levels during these seasons. In contrast, not only were corticosterone levels higher during breeding, but adrenals further responded to an exogenous ACTH signal, indicating a dramatic enhancement of the adrenal's ability to secrete corticosterone. Furthermore, we inferred the pituitary's ACTH secretory ability by injecting exogenous corticotrophin-releasing factor (CRF), arginine vasotocin (AVT) and mesotocin and measured corticosterone release. Pituitaries in breeding birds appear to respond to exogenous CRF and AVT, suggesting hypothalamic control of corticosterone release during this season. Taken together, these results suggest that seasonal modulation of corticosterone release in this species is controlled primarily at the adrenal.

Effects of exogenous arginine vasotocin on circulating levels of thyroid hormones and melatonin in the pigeon, Columbia livia

The effects of intravenous injections of two different preparations of synthetic arginine vasotocin (AVT), deamino-dicarba-arginine vasotocin and arginine vasotocin diacetate tetrahydrate on serum levels of thyroxine (T 4), triiodothyronine (T 3) and melatonin were studied in the resting pigeon. Although variations depending on factors such as the type of AVT preparation and the dose used and also the duration of treatment were apparent, both preparations of AVT produced an increase in serum levels of T 4 and a decrease in that of T 3. The T 3: T 4 ratio was also significantly lower in response to AVT administration. However, no statistically significant changes in serum levels of melatonin were discernible with the administration of either of the two AVT preparations, even though melatonin levels in most AVT-treated groups showed a trend ( P > 0.05) to be higher than that in the controls. The rise in T 4 levels is indicative of increased release of T 4 and/or the inhibition of its conversion to the active hormone, T 3. The drop in T 3 may account for the AVT-induced reduction in the metabolic rate of the pigeon observed in an earlier study. The absence of a significant increase in melatonin indicates that AVT could not produce such a change in the daytime in resting pigeons, in contrast to that in flown homing pigeons, suggesting that the modulating effect of AVT on melatonin levels is dependent on the physiological state of the animal.

Effect of breeding state, moulting, dehydration, exposure to saturated atmosphere, and arginine vasotocin on cutaneous water permeability in the toad Bufo bufo

Cutaneous water permeability was assessed in hydrated male toads under a variety of conditions, including dehydration and rehydration, and the effects of exogenous arginine vasotocin (AVT) were determined. Cutaneous water permeability (the rate of water uptake by toads in water) was high in toads collected in the breeding pond and declined steeply during the first week, coincident with reduced activity of the cutaneous mucus glands. The slopes of the dose-response curves relating AVT to cutaneous-water influx were about the same at the transition from the breeding to the nonbreeding state, but the level of influx was higher in the breeding state. The dose-response relationship in long-term terrestrial-acclimated toads was similar to that in water-acclimated toads. The threshold dose for effect on the cutaneous water permeability was about 1 mg AVT. Dehydration had a substantially greater effect on the cutaneous water permeability than AVT. The ratio between dehydration and AVT responses tended to increase with increasing water transport capacity of the skin. Moulting and acclimation to a saturated atmosphere in fully hydrated toads more than doubled the water permeability and abolished the response to AVT. It is suggested that AVT and other factors increase the cutaneous water permeability by similar mechanisms, such as insertion of water channels in the apical membrane of the epidermal cells. The effect of AVT on the toad skin is interpreted as reflecting the general high potency of neurohypophysial hormones in stimulating the water permeability of membranes of variable permeability.

Effects of arginine vasotocin, cortisol and adrenergic factors on water balance in the toad Bufo bufo: Physiology or pharmacology?

1. 1. The threshold level of exogenous arginine vasotocin (AVT) for increasing the cutaneous water permeability in Bufo bufo was several times higher than has been measured in dehydrated frogs and toads. 2. 2. The β-agonist isoproterenol was without effect on water balance in hydrated toads but increased the response to large doses of AVT by 25–50%. 3. 3. Implantation of cortisol pellets in water-acclimated toads enhanced the cutaneous water permeability by a factor of 2–3. 4. 4. It is concluded that understanding of water balance in terrestrial anurans may depend upon the unravelling of mechanisms that integrate cutaneous water transport and diuresis.

Water balance responses of the hylid frog Litoria aurea

AbstractCutaneous and antidiuretic water balance responses of the hylid frog Litoria aurea to dehydration and exogenous arginine vasotocin (AVT) were examined. Both dehydration and AVT caused an increase in the rate of water uptake through ventral skin. Dehydration (in one of two experiments) and AVT also caused a reduction in the rate of bladder urine accumulation. During rehydration, rates of water uptake through ventral skin were seven times higher than through the average body surface of immersed frogs. Treatment of normally hydrated frogs with AVT in vivo caused increased cutaneous water uptake and a reduction in glomerular filtration rate; together these produced water retention equivalent to 27% above original body weight. Pelvic skin had a higher resting rate of osmotic water flow (OWF) in vitro than did pectoral or dorsal skin and was the only region to show increased OWF in response to AVT. The cutaneous hydroosmotic response of L. aurea to AVT is unusually large for a semiaquatic frog, and this may reflect the basking habits of this species or its position within the Hylidae.

Evolution of Neurohypophyseal Hormone Actions in Vertebrates

Arginine vasotocin (AVT) is one neurohypophyseal principle that has been found in all vertebrates including the cyclostomes. Although many effects have been seen with administered AVT in many vertebrate species, the physiological role of endogenous AVT is largely unknown. In this review, the evolution of the renal and vascular actions of AVT are discussed. Injection of AVT produces diuresis in teleosts and lungfishes, but antidiuresis in tetrapods. In fishes and all tetrapods except birds, AVT is hypertensive. We have proposed that the renal responses can in fact be explained by the vascular responses. In our hypothesis, there are four types of responses to AVT. In type I, the peripheral vasculature is more responsive to AVT than the renal preglomerular arteriole so that AVT will cause a significant rise in systemic blood pressure and a net increase in the glomerular perfusion. This will then result in diuretic and pressor responses. Teleosts and lungfishes belong to this type. Type 11 is exemplified by the mudpuppy which responds to AVT with antidiuresis and blood pressure increase. This can be explained by an increase in sensitivity to AVT by the preglomerular arteriole so that AVT will cause a decrease in glomerular perfusion even when systemic blood pressure is increased. In type III which can be seen in the bullfrog, the vascular response to AVT will produce glomerular antidiuresis and blood pressure increase. In addition, tubular receptors for AVT are also present and these receptors are involved in the tubular reabsorption of water, thus enhancing the antidiuretic response. Type IV as seen in mammals is mainly a tubular antidiuretic response to ADH. Evidence in support of this hypothesis is given in the paper. The above discussion concerns the renal and vascular actions of exogenous AVT. Our studies so far indicate that endogenous AVT is not the major regulatory mechanism in renal and vascular functions of the lungfish or bullfrog, although it may have a modulatory role.

Aspects of renal function in the lizard Varanus gouldii

1. 1. Renal function was studied in Varanus gouldii under control, water-loaded and salt-loaded conditions and the effects of exogenous arginine vasotocin (AVT) were also noted. 2. 2. Glomerular filtration rate (GFR) in V. gouldii was similar to that of other reptiles. GFR increased substantially with water-loading but decreased when AVT was injected. Salt-loading did not affect GFR significantly. 3. 3. There were no pronounced tubular effects with water-loading or AVT administration but there was increased resorption of water with salt-loading. 4. 4. A constant percentage of filtered sodium was resorbed in all treatments. 5. 5. The kidneys exhibited a limited degree of control over water and electrolyte excretion and this is discussed in relation to the functions of the cloaca and nasal salt glands.