Vasopressin Abstracts 1


Neuromodulation of memory in the hippocampus by vasopressin
            (Alescio-Lautier et al., 2000) Download
The involvement of [Arg(8)]vasopressin in memory processes was analyzed in the hippocampal structure, since we have reported that this is one of the main central target structures of the vasopressin-enhancing effect on memory. This structure is functionally differentiated along its dorsoventral axis, and the expression of the vasopressinergic system is dependent upon whether the dorsal or ventral part of the hippocampus is involved. For this reason, the effect of vasopressin injected into hippocampus was evaluated on the basis of the site of injection. We have shown, using a Go-No Go visual discrimination task with mice that both parts of the hippocampus are involved in the effect of endogenous or exogenous vasopressin, but with higher sensitivity for the ventral part. Based on the expression of Fos protein following intracerebroventricular injection of vasopressin in unconditioned or conditioned mice, we confirmed the greater involvement of the ventral hippocampus in the enhancing effect of vasopressin on memory processes. The effect of the peptide seems specific, since only a few of the hippocampal cells that expressed Fos protein in the unconditioned mice did so in the conditioned mice (cells in the dentate gyrus and the CA3 hippocampal field). Moreover, we have shown that in the ventral hippocampus, vasopressin generates different behavioral effects whether treatment is performed at the beginning or in the middle of the learning process, suggesting that the mnemonic context is an important factor for understanding the effect of vasopressin on memory in the ventral hippocampus.

Catecholamines and vasopressin during critical illness
            (Bassi et al., 2006) Download
This article summarizes the effects of catecholamines and vasopressin on the cardiovascular system, focusing on their metabolic and immunologic properties. Particular attention is dedicated to the septic shock condition.

Vasopressin increases human risky cooperative behavior.
            (Brunnlieb et al., 2016) Download
The history of humankind is an epic of cooperation, which is ubiquitous across societies and increasing in scale. Much human cooperation occurs where it is risky to cooperate for mutual benefit because successful cooperation depends on a sufficient level of cooperation by others. Here we show that arginine vasopressin (AVP), a neuropeptide that mediates complex mammalian social behaviors such as pair bonding, social recognition and aggression causally increases humans' willingness to engage in risky, mutually beneficial cooperation. In two double-blind experiments, male participants received either AVP or placebo intranasally and made decisions with financial consequences in the "Stag hunt" cooperation game. AVP increases humans' willingness to cooperate. That increase is not due to an increase in the general willingness to bear risks or to altruistically help others. Using functional brain imaging, we show that, when subjects make the risky Stag choice, AVP down-regulates the BOLD signal in the left dorsolateral prefrontal cortex (dlPFC), a risk-integration region, and increases the left dlPFC functional connectivity with the ventral pallidum, an AVP receptor-rich region previously associated with AVP-mediated social reward processing in mammals. These findings show a previously unidentified causal role for AVP in social approach behavior in humans, as established by animal research.

Vasopressin: behavioral roles of an "original" neuropeptide
            (Caldwell et al., 2008) Download
Vasopressin (Avp) is mainly synthesized in the magnocellular cells of the hypothalamic supraoptic (SON) and paraventricular nuclei (PVN) whose axons project to the posterior pituitary. Avp is then released into the blood stream upon appropriate stimulation (e.g., hemorrhage or dehydration) to act at the kidneys and blood vessels. The brain also contains several populations of smaller, parvocellular neurons whose projections remain within the brain. These populations are located within the PVN, bed nucleus of the stria terminalis (BNST), medial amygdala (MeA) and suprachiasmatic nucleus (SCN). Since the 1950s, research examining the roles of Avp in the brain and periphery has intensified. The development of specific agonists and antagonists for Avp receptors has allowed for a better elucidation of its contributions to physiology and behavior. Anatomical, pharmacological and transgenic, including "knockout," animal studies have implicated Avp in the regulation of various social behaviors across species. Avp plays a prominent role in the regulation of aggression, generally of facilitating or promoting it. Affiliation and certain aspects of pair-bonding are also influenced by Avp. Memory, one of the first brain functions of Avp that was investigated, has been implicated especially strongly in social recognition. The roles of Avp in stress, anxiety, and depressive states are areas of active exploration. In this review, we concentrate on the scientific progress that has been made in understanding the role of Avp in regulating these and other behaviors across species. We also discuss the implications for human behavior.


Lysine vasopressin in post-traumatic memory disorders: an uncontrolled pilot study.
            (Eames and Wood, 1999) Download
Thirteen severely head-injured individuals undergoing residential rehabilitation were willing to take part. Subsequently, 13 out-patients (OP) referred for pre- admission or medico-legal assessment were recruited. Treatment consisted of Syntopressin Nasal Spray (8-lysine-vasopressin, Sandoz), one squirt (approximately 4 units) to each nostril, twice a day for about 1 month. Effectively, this meant the delivery of some 500 units (two spray bottles) in all. The maximum time from first to second assessment was 2 months. Comparisons (2- tailed t-tests), both for individual tests and for the total scores between sub-groups divided by IP/OP status or sex, or about the mean for age, PTA, time since injury or severity of initial cognitive deficits (i.e. initial total score), showed no statistically significant differences. On multiple regression analysis there were no significant F scores relating to the effects of any of these factors, or any combination of them, on the degree of improvement. Similarly, there were no significant correlations from analysis of covariance, except for a rather weak effect (T = ­ 1.807, p = 0.029) of PTA on the initial score on Logical Memory in the Delayed condition. There was one qualitative feature that seemed of potential interest, but unfortunately was not recorded routinely. Either the patient or relatives reported improvements in alertness and memory in some of those who showed no measurable Lysine vasopressin in memory disorders 259 changes, whilst in several of those whose scores did change significantly, no such subjective improvements were claimed.

Arginine vasopressin improves the memory deficits in Han Chinese patients with first-episode schizophrenia.
            (Geng et al., 2017) Download
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.

Effects of 1-desamo-8-D-arginine vasopressin on behaviour and cognition in primary affective disorder.
            (Gold et al., 1979) Download
DDAVP (1-desamino-8-d-arginine vasopressin), a synthetic analogue of vasopressin with prolonged half-life and high antidiuretic and low pressor activity, was given in a double-blind placebo-controlled trial to four patients with major affective illness. Three of four patients showed highly significant and consistent improvements in tests designed to measure the formation, encoding, and organisation of long-term trace events in memory. Two patients also showed a significant but less consistent amelioration of other depressive symptoms during DDAVP treatment. These findings implicate central vasopressin function in the processing of information and possibly other aspects of affective illness.

Effects of arginine vasopressin on musical working memory.
            (Granot et al., 2013) Download
Previous genetic studies showed an association between variations in the gene coding for the 1a receptor of the neuro-hormone arginine vasopressin (AVP) and musical working memory (WM). The current study set out to test the influence of intranasal administration (INA) of AVP on musical as compared to verbal WM using a double blind crossover (AVP-placebo) design. Two groups of 25 males were exposed to 20 IU of AVP in one session, and 20 IU of saline water (placebo) in a second session, 1 week apart. In each session subjects completed the tonal subtest from Gordon's "Musical Aptitude Profile," the interval subtest from the "Montreal Battery for Evaluation of Amusias (MBEA)," and the forward and backward digit span tests. Scores in the digit span tests were not influenced by AVP. In contrast, in the music tests there was an AVP effect. In the MBEA test, scores for the group receiving placebo in the first session (PV) were higher than for the group receiving vasopressin in the first session (VP) (p < 0.05) with no main Session effect nor Group × Session interaction. In the Gordon test there was a main Session effect (p < 0.05) with scores higher in the second as compared to the first session, a marginal main Group effect (p = 0.093) and a marginal Group × Session interaction (p = 0.88). In addition we found that the group that received AVP in the first session scored higher on scales indicative of happiness, and alertness on the positive and negative affect scale, (PANAS). Only in this group and only in the music test these scores were significantly correlated with memory scores. Together the results reflect a complex interaction between AVP, musical memory, arousal, and contextual effects such as session, and base levels of memory. The results are interpreted in light of music's universal use as a means to modulate arousal on the one hand, and AVP's influence on mood, arousal, and social interactions on the other.

Vasopressin: a review of therapeutic applications
            (Holt and Haspel, 2010) Download
Vasopressin (vp) was discovered in 1895 from the extract of the posterior pituitary and named for the early observation of its vasoconstrictive properties.1 The peptide is present in various species, both invertebrate and vertebrate, with only minor variations in amino acid se- quence. Human VP contains the amino acid arginine, hence the name arginine vasopressin. It is alternatively referred to as antidiuretic hormone (ADH), reflecting its main physio- logic function in promoting water retention. (For the remain- der of the text, the term vasopressin and the abbreviation VP will be used in lieu of arginine vasopressin or antidiuretic hormone.)

Vasopressin in post-traumatic amnesia
            (Koch-Henriksen and Nielsen, 1981) Download
Because memory impairment after severe head injury is common and carries serious psychological and social consequences, we decided to carry out a double-blind trial to assess the effect of vasopressin on memory in patients with pronounced mental disabilities after severe head injuries.We planned to include 30 volunteers, 15 on vasopressin and 15 on placebo. The first 8 patients passed through the treatment without any improvement.N ochanges were found in performance, assessed by the psychological tests, and our general impression of the mental condition of the patients was unaltered. No patient reported subjective benefit from the treatment, when asked immediately afterwards and 4weeks later.No side-effects were reported. We decided not to carry on with the trial, concluding that there would be a remote chance of benefit from vasopressin in this type of patient, and not enough to justify the cost of completing the trial.

Influence of vasopressin on learning and memory.
            (Legros et al., 1978) Download
Since memory disorders are a frequent complaint in ageing people, we studied the influence of exogenous vasopressin on learning and memory in men aged 50-65. Twenty-three inpatients with minor pulmonary or gastroenterological diseases volunteered for this study. The study was done double-blind with random allocation to a regimen of approximately 16 i.u. of lysine-8-vasopressin (’Vasopressin-Sandoz’) daily (one puff to each nostril three times a day) for 3 days or a placebo (solvent alone) by the same route. Eleven patients received the placebo and twelve vasopressin. No significant change was noted in the clinical or biochemical data measured after treatment with vasopressin or placebo. However, the psychometric tests revealed significant differences between the two groups after treatment. Results favoured vasopressin. We conclude that patients given vasopressin performed better in tests involving attention, concentration, and motor rapidity -(K.T. attention test and W.A.I.S. digit symbol test) and better in memory tests using Rey’s visual-graphic material for the measurement of visual retention, recognition, and recall; vasopressin also improved attention and immediate memory (W.A.I.S. digit span) and learning and recognition (15 words of Rey).

Vasopressin in amnesia.
            (Oliveros et al., 1978) Download
We have treated four patients with amnesia with vasopressin nasal spray (’Vasopressin-Sandoz’). These pilot studies are encouraging and suggest the need for a controlled trial

Verbal memory after three months of intranasal vasopressin in healthy old humans.
            (Perras et al., 1997) Download
In animals, evidence has been accumulated that vasopressin (VP) improves learning and memory. In humans, this effect was not consistently demonstrated, and attempts to restore age-related memory deficits by VP also remained inconsistent. Assuming that in old subjects a beneficial effect on memory occurs only after prolonged treatment with VP, we conducted a study in 26 healthy elderly persons receiving 40 IU of VP for three months through the intranasal route. The trial was randomized, placebo-controlled and held double-blind. Memory was assessed by the Auditory Verbal Learning Test (AVLT) requiring the subject to learn repeatedly presented lists of 15 words. Results demonstrated no general effect of long-term treatment with VP on memory in aged humans. However, recall of an interfering word list was improved, indicating a diminished proactive interference by the peptide. Additionally, VP influenced recall depending on the serial position of an item: it improved the primacy effect (i.e. recall of the first words of a list) and impaired the recency effect. This result may indicate an improved semantic encoding (i.e. a primary effect on processes of attention) after long-term administration of VP.


Dose-Dependent and Lasting Influences of Intranasal Vasopressin on Face Processing in Men.
            (Price et al., 2017) Download
Arginine vasopressin (AVP) and related peptides have diverse effects on social behaviors in vertebrates, sometimes promoting affiliative interactions and sometimes aggressive or antisocial responses. The type of influence, in at least some species, depends on social contexts, including the sex of the individuals in the interaction and/or on the levels of peptide within brain circuits that control the behaviors. To determine if AVP promotes different responses to same- and other-sex faces in men, and if those effects are dose dependent, we measured the effects of two doses of AVP on subjective ratings of male and female faces. We also tested if any influences persist beyond the time of drug delivery. When AVP was administered intranasally on an initial test day, 20 IU was associated with decreased social assessments relative to placebo and 40 IU, and some of the effects persisted beyond the initial drug delivery and appeared to generalize to novel faces on subsequent test days. In single men, those influences were most pronounced, but not exclusive, for male faces, whereas in coupled men they were primarily associated with responses to female faces. Similar influences were not observed if AVP was delivered after placebo on a second test day. In a preliminary analysis, the differences in social assessments observed between men who received 20 and 40 IU, which we suggest primarily reflect lowered social assessments induced by the lower dose, appeared most pronounced in subjects who carry what has been identified as a risk allele for the V1a receptor gene. Together, these results suggest that AVP's effects on face processing, and possibly other social responses, differ according to dose, depend on relationship status, and may be more prolonged than previously recognized.

Arginine Vasopressin Effects on Subjective Judgments and Neural Responses to Same and Other-Sex Faces in Men and Women.
            (Rilling et al., 2017) Download
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.

Estrogen receptors: their roles in regulation of vasopressin release for maintenance of fluid and electrolyte homeostasis
            (Sladek and Somponpun, 2008) Download
Long standing interest in the impact of gonadal steroid hormones on fluid and electrolyte balance has led to a body of literature filled with conflicting reports about gender differences, the effects of gonadectomy, hormone replacement, and reproductive cycles on plasma vasopressin (VP), VP secretion, and VP gene expression. This reflects the complexity of gonadal steroid hormone actions in the body resulting from multiple sites of action that impact fluid and electrolyte balance (e.g. VP target organs, afferent pathways regulating the VP neurons, and the VP secreting neurons themselves). It also reflects involvement of multiple types of estrogen receptors (ER) in these diverse sites including ERs that act as transcription factors regulating gene expression (i.e. the classic ERalpha as well as the more recently discovered ERbeta) and potentially G-protein coupled, membrane localized ERs that mediate rapid non-genomic actions of estrogen. Furthermore, altered expression of these receptors in physiologically diverse conditions of fluid and electrolyte balance contributes to the difficulty of using simplistic approaches such as gender comparisons, gonadectomy, and hormone replacement to assess the role of gonadal steroids in regulation of VP secretion for maintenance of fluid and electrolyte homeostasis. This review catalogs these inconsistencies and provides a frame work for understanding them by describing: (1) the effect of gonadal steroids on target organ responsiveness to VP; (2) the expression of multiple types of estrogen receptors in the VP neurons and in brain regions monitoring feedback signals from the periphery; and (3) the impact of dehydration and hyponatremia on expression of these receptors.



Alescio-Lautier, B, V Paban, and B Soumireu-Mourat (2000), ‘Neuromodulation of memory in the hippocampus by vasopressin.’, Eur J Pharmacol, 405 (1-3), 63-72. PubMed: 11033315
Bassi, G, P Radermacher, and E Calzia (2006), ‘Catecholamines and vasopressin during critical illness.’, Endocrinol Metab Clin North Am, 35 (4), 839-57, x. PubMed: 17127150
Brunnlieb, C, et al. (2016), ‘Vasopressin increases human risky cooperative behavior.’, Proc Natl Acad Sci U S A, 113 (8), 2051-56. PubMed: 26858433
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Geng, CH, et al. (2017), ‘Arginine vasopressin improves the memory deficits in Han Chinese patients with first-episode schizophrenia.’, Peptides, 97 8-15. PubMed: 28882471
Gold, PW, et al. (1979), ‘Effects of 1-desamo-8-D-arginine vasopressin on behaviour and cognition in primary affective disorder.’, Lancet, 2 (8150), 992-94. PubMed: 91778
Granot, RY, et al. (2013), ‘Effects of arginine vasopressin on musical working memory.’, Front Psychol, 4 712. PubMed: 24151474
Holt, NF and KL Haspel (2010), ‘Vasopressin: a review of therapeutic applications.’, J Cardiothorac Vasc Anesth, 24 (2), 330-47. PubMed: 19945299
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Legros, JJ, et al. (1978), ‘Influence of vasopressin on learning and memory.’, Lancet, 1 (8054), 41-42. PubMed: 74519
Oliveros, JC, et al. (1978), ‘Vasopressin in amnesia.’, Lancet, 1 (8054), 42. PubMed: 74520
Perras, B, et al. (1997), ‘Verbal memory after three months of intranasal vasopressin in healthy old humans.’, Psychoneuroendocrinology, 22 (6), 387-96. PubMed: 9364618
Price, D, et al. (2017), ‘Dose-Dependent and Lasting Influences of Intranasal Vasopressin on Face Processing in Men.’, Front Endocrinol (Lausanne), 8 220. PubMed: 29018407
Rilling, JK, et al. (2017), ‘Arginine Vasopressin Effects on Subjective Judgments and Neural Responses to Same and Other-Sex Faces in Men and Women.’, Front Endocrinol (Lausanne), 8 200. PubMed: 28871239
Sladek, CD and SJ Somponpun (2008), ‘Estrogen receptors: their roles in regulation of vasopressin release for maintenance of fluid and electrolyte homeostasis.’, Front Neuroendocrinol, 29 (1), 114-27. PubMed: 18022678