Oxytocin

From Wikipedia, the free encyclopedia

Oxytocin

Systematic (IUPAC) name

1-({(4R,7S,10S,13S,16S,19R)-19-amino-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-16-(4-hydroxybenzoyl)13-[(1S)-1-methylpropyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentaazacycloicosan-4-yl}carbonyl)-Lprolyl-L-leucylglycinamide

Clinical data

Trade names

Pitocin

AHFS/Drugs.com

monograph

Pregnancy cat.

(AU)

Legal status

POM

(UK) -only (US)

Routes

Intranasal, IV, IM

Pharmacokinetic data

Bioavailability

nil

Protein binding

30%

Metabolism

hepatic oxytocinases

Half-life

16 min

Excretion

Biliary and renal

Identifiers

CAS number

50-56-6

ATC code

H01BB02

PubChem

CID 439302

IUPHAR ligand

2174

DrugBank

DB00107

ChemSpider

388434

UNII

1JQS135EYN

KEGG

D00089

ChEBI

CHEBI:7872

ChEMBL

CHEMBL395429

Chemical data

Formula

C43H66N12O12S2

Mol. mass

1007.19 g/mol

SMILES[show]

InChI[show]

(what is this?) (verify)

Oxytocin (Oxt) /kstosn/ is a mammalian neurohypophysial hormone, (secreted by the posterior pituitary gland), that acts primarily as a neuromodulator in the brain.

Oxytocin plays an important role in the neuroanatomy of intimacy, specifically in sexual reproduction, in particular during and after childbirth. It is released in large amounts after distension of the cervix and uterus during labor, facilitating birth,maternal bonding, and, after stimulation of the nipples, lactation. Both childbirth and milk ejection result from positive feedback mechanisms.[1]

Recent studies have begun to investigate oxytocin's role in various behaviors, including orgasm, social recognition, pair bonding, anxiety, and maternal behaviors.[2] For this reason, it is

sometimes referred to as the "bonding hormone". There is some evidence that oxytocin promotes ethnocentric behavior, incorporating the trust and empathy of in-groups with their suspicion and rejection of outsiders.[3] Furthermore, genetic differences in the oxytocin receptor gene (OXTR) have been associated with maladaptive social traits such as aggressive behaviour. [4]

Contents

[hide]

1 Discovery

2 Structure and relation to vasopressin

3 Actions

o o

3.1 Peripheral (hormonal) actions

3.2 Actions within the brain

4 Drug forms

4.1 Potential adverse reactions

5 Synthesis, storage, and release

o o

5.1 Neural sources

5.2 Non-neural sources

Discovery
6 Evolution

5.2.1 Female

5.2.2 Male

7 Role of Oxytocin in Fear and Anxiety Response

8 See also

9 References

10 Further reading

11 External links

[edit]

The word oxytocin was coined from the term oxytocic (used at least in the 1800s to refer to agents such as ergots that would cause uterine simulation; Greek , oxys, and , tokos, meaning "quick birth") by chemists at Parke, Davis, and Company around 1927,[5] two decades after its uterine-contracting properties were discovered by British pharmacologist Sir Henry Hallett Dale in 1906.[6] The milk ejection property of oxytocin was described by Ott and Scott in 1910[7] and by Schafer and Mackenzie in 1911.[8]

The nine amino acid sequence of oxytocin was elucidated by Vincent du Vigneaud et al. and by Tuppy in 1953[9] and synthesized biochemically soon after by du Vigneaud et al. in 1953.[10][11] Oxytocin was the first polypeptide hormone to be sequenced and synthesized.[12]

Structure and relation to vasopressin

[edit]

Oxytocin is a peptide of nine amino acids (a nonapeptide). Its systematic name is cysteine-tyrosine-isoleucine-glutamine-asparagine-cysteine-proline-leucine-glycine-amide (cys tyr ile gln asn cys pro leu gly NH2, or CYIQNCPLG-NH2). Oxytocin has a molecular mass of 1007 daltons. One international unit (IU) of oxytocin is the equivalent of about 2 micrograms of

pure peptide. While the structure of oxytocin is highly conserved in placental mammals, a novel structure of oxytocin was recently reported in marmosets, tamarins, and other new

world primates. Genomic sequencing of the gene for oxytocin revealed a single in-frame mutation (thymine for cytosine) which results in a single amino acid substitution at the 8-position (proline for leucine).[13]

The biologically active form of oxytocin, commonly measured by RIA and/or HPLC techniques, is also known as the octapeptide "oxytocin disulfide" (oxidized form), but oxytocin also exists as a reduced dithiol nonapeptide called oxytoceine.[14] It has been theorized that open chain oxytoceine (the reduced form of oxytocin) may also act as a free radical scavenger (by donating an
[15]

electron to a free radical); oxytoceine may then be oxidized back to oxytocin via the redox potential of dehydroascorbate <---> ascorbate.

Oxytocin (ball-and-stick) bound to its carrier protein neurophysin (ribbons)

The structure of oxytocin is very similar to that of vasopressin (cys tyr phe gln asn cys pro arg gly NH2), also a nonapeptide with a sulfur bridge, whose sequence differs from

oxytocin by two amino acids. A table showing the sequences of members of the vasopressin/oxytocin superfamily and the species expressing them is present in the vasopressin article.

Oxytocin and vasopressin were isolated and synthesized by Vincent du Vigneaud in 1953, work for which he received the Nobel Prize in Chemistry in 1955.

Oxytocin and vasopressin are the only known hormones released by the human posterior pituitary gland to act at a distance. However, oxytocin neurons make other peptides,

includingcorticotropin-releasing hormone and dynorphin, for example, that act locally. The magnocellular neurosecretory cells that make oxytocin are adjacent to magnocellular neurosecretory

cells that make vasopressin. These are large neuroendocrine neurons which are excitable and can generate action potentials.

Actions

[edit]

Oxytocin has peripheral (hormonal) actions, and also has actions in the brain. Its actions are mediated by specific, high-affinity oxytocin receptors. The oxytocin receptor is a G-protein-coupled receptor that requires Mg2+ and cholesterol. It belongs to the rhodopsin-type (class I) group of G-protein-coupled receptors.

Peripheral (hormonal) actions

[edit]

The peripheral actions of oxytocin mainly reflect secretion from the pituitary gland. (See oxytocin receptor for more detail on its action.)

Letdown reflex: In lactating (breastfeeding) mothers, oxytocin acts at the mammary glands, causing milk to be 'let down' into subareolar sinuses, from where it can be excreted via the nipple.[16] Suckling by the infant at the nipple is relayed by

spinal nerves to the hypothalamus. The stimulation causes neurons that make oxytocin to fire action potentials in

intermittent bursts; these bursts result in the secretion of pulses of oxytocin from the neurosecretory nerve terminals of the

pituitary gland.

Uterine contraction: Important for cervical dilation before birth, oxytocin causes contractions during the second and third

stages of labor. Oxytocin release during breastfeeding causes mild but often painful contractions during the first few weeks

of lactation. This also serves to assist the uterus in clotting the placental attachment point postpartum. However, in knockout mice lacking the oxytocin receptor, reproductive behavior and parturition are normal.[17]

Social behavior[18][19] and wound healing: Oxytocin is also thought to modulate inflammation by decreasing certain cytokines.

Thus, the increased release in oxytocin following positive social interactions has the potential to improve wound healing. A

study by Marazziti and colleagues used heterosexual couples to address this possibility. They found increases in plasma

oxytocin following a social interaction were correlated with faster wound healing. They hypothesized this was due to

oxytocin reducing inflammation, thus allowing the wound to heal faster. This study provides preliminary evidence that positive social interactions may directly impact aspects of health.[20]

The relationship between oxytocin and human sexual response is unclear. At least two uncontrolled studies have found increases in plasma oxytocin at orgasm in both men and women.[21][22] Plasma oxytocin levels are notably increased

around the time of self-stimulated orgasm and are still higher than baseline when measured five minutes after self
[21]

arousal.

The authors of one of these studies speculated that oxytocin's effects on muscle contractibility may facilitate

sperm and egg transport.[21]

In a study measuring oxytocin serum levels in women before and after sexual stimulation, the author suggests it

serves an important role in sexual arousal. This study foundgenital tract stimulation resulted in increased oxytocin immediately after orgasm.[23] Another study reported increases of oxytocin during sexual arousal could be in response to nipple/areola, genital, and/or genital tract stimulation as confirmed in other mammals. [24] Murphy et al.

(1987), studying men, found oxytocin levels were raised throughout sexual arousal with no acute increase at
[25]

orgasm.

A more recent study of men found an increase in plasma oxytocin immediately after orgasm, but only in a

portion of their sample that did not reach statistical significance. The authors noted these changes "may simply reflect contractile properties on reproductive tissue".[26]

Oxytocin evokes feelings of contentment, reductions in anxiety, and feelings of calmness and security around the
[27]

mate.

This suggests oxytocin may be important for the inhibition of the brain regions associated with behavioral

control, fear, and anxiety, thus allowing orgasm to occur. Oxytocin also functions to protect against stress. Meta-

analyses conducted in 2003 demonstrated that oxytocin can alleviate mood and reduce stress with a good
[28]

efficiency.

Due to its similarity to vasopressin, it can reduce the excretion of urine slightly. In several species,

oxytocin can stimulate sodium excretion from the kidneys (natriuresis), and, in humans, high doses can

result in hyponatremia.

Oxytocin and oxytocin receptors are also found in the heart in some rodents, and the hormone may play a role in the embryonal development of the heart by promotingcardiomyocyte differentiation.[29][30] However,

the absence of either oxytocin or its receptor in knockout mice has not been reported to produce cardiac
[17]

insufficiencies.

Modulation of hypothalamic-pituitary-adrenal axis activity: Oxytocin, under certain circumstances, indirectly

inhibits release of adrenocorticotropic hormone and cortisol and, in those situations, may be considered an antagonist of vasopressin.[31]

Autism: Oxytocin may play a role in autism and may be an effective treatment for autism's repetitive and
[32]

affiliative behaviors.

Oxytocin treatments also resulted in an increased retention of affective speech in

adults with autism.[33] Two related studies in adults, in 2003 and 2007, found oxytocin decreased repetitive

behaviors and improved interpretation of emotions. More recently, intranasal administration of oxytocin

was found to increase emotion recognition in children as young as 12 who are diagnosed with autism spectrum disorders.[34] Oxytocin has also been implicated in the etiology of autism, with one report

suggesting autism is correlated with genomic deletion of the gene containing the oxytocin receptor gene

(OXTR). Studies involving Caucasian and Finnish samples and Chinese Han families provide support for the relationship of OXTR with autism.[33][35] Autism may also be associated with an aberrant methylation of OXTR.[33] After treatment with inhaled oxytocin, autistic patients exhibit more appropriate social
[36]

behavior.

While this research suggests some promise, further clinical trials of oxytocin are required to

demonstrate potential benefit and side effects in the treatment of autism. As such, researchers do not recommend use of oxytocin as a treatment for autism outside of clinical trials.[37]

Increasing trust and reducing fear: In a risky investment game, experimental subjects given nasally

administered oxytocin displayed "the highest level of trust" twice as often as the control group. Subjects

who were told they were interacting with a computer showed no such reaction, leading to the conclusion
[38]

that oxytocin was not merely affecting risk aversion.

Nasally administered oxytocin has also been

reported to reduce fear, possibly by inhibiting the amygdala (which is thought to be responsible for fear
[39]

responses).

Indeed, studies in rodents have shown oxytocin can efficiently inhibit fear responses by

activating an inhibitory circuit within the amygdala. Some researchers have argued oxytocin has a general

enhancing effect on all social emotions, since intranasal administration of oxytocin also increases envy and Schadenfreude.[40]

Trust is increased by oxytocin.

[41][42][43]

Disclosure of emotional events is a sign of trust in humans. When

recanting a negative event, humans that receive intranasal oxytocin share more emotional details and stories with more emotional significance.[42] Humans also find faces more trustworthy after receiving

intranasal oxytocin. In a study, participants that received intranasal oxytocin viewed photographs of human

faces with neutral expressions and found them to be more trustworthy than those who did not receive oxytocin.[41] This may be because oxytocin reduces the fear of social betrayal in humans.[44] Even after

experiencing social alienation by being excluded from a conversation, humans that received oxytocin scored higher in trust on the Revised NEO Personality Inventory.[43]

While Oxytocin increases trust,[41][42][43] it does so only to a certain degree. In a study, participants played a variation of the trust game and acted as an investor, deciding how much money to allocate to a trustee. [45] The trustee was described as trustworthy, untrustworthy, or neutral. Participants that

received intranasal oxytocin gave more money to the trustworthy and neutral trustees. Participants that

received oxytocin did not give more money to the untrustworthy trustee, implying that oxytocin only increases trust when there is no reason to be distrustful.[43] When there is a reason to be distrustful, such

as experiencing betrayal, differing reactions are associated with oxytocin receptor gene(OXTR)

differences. Those with the CT haplotype experience a stronger reaction, in the form of anger, to betrayal.[46]

Oxytocin affects social distance between adult males and females, and may be responsible at least in part

for romantic attraction and subsequent monogamous pair bonding. An oxytocin nasal spray caused men in

a monogamous relationship, but not single men, to increase the distance between themselves and an

attractive woman during a first encounter by 10 to 15 centimeters. The researchers suggested that
[47]

oxytocin may help promote fidelity within monogamous relationships.

Affecting generosity by increasing empathy during perspective taking: In

a neuroeconomics experiment, intranasal oxytocin increased generosity in the Ultimatum Game by 80%,

but had no effect in the Dictator Game that measures altruism. Perspective-taking is not required in the

Dictator Game, but the researchers in this experiment explicitly induced perspective-taking in the Ultimatum Game by not identifying to participants into which role they would be placed. [48] Serious

methodological questions have arisen, however, with regard to the role of oxytocin in trust and generosity.[49]

Empathy in healthy males has been shown to be increased after intranasal oxytocin[50][51] This is most likely due to the effect of oxytocin in enhancing eye gaze.[52] There is some discussion about which aspect of empathy oxytocin might alter for example, cognitive vs. emotional empathy.[53]

Cognitive function: Certain learning and memory functions are impaired by centrally administered
[54]

oxytocin.

Also, systemic oxytocin administration can impair memory retrieval in certain aversive
[55]

memory tasks.

Interestingly, oxytocin does seem to facilitate learning and memory specifically

for social information. Healthy males administered intranasal oxytocin show improved memory for
[56][57]

human faces, in particular happy faces.

They also show improved recognition for positive and improved recognition of fear.[60]

social cues over threatening social cues

[58][59]

Actions within the brain

[edit]

Oxytocin secreted from the pituitary gland cannot re-enter the brain because of the bloodbrain barrier.

Instead, the behavioral effects of oxytocin are thought to reflect release from centrally projecting oxytocin

neurons, different from those that project to the pituitary gland, or that are collaterals from them.[61] Oxytocin receptors are expressed by neurons in many parts of the brain and spinal cord, including

the amygdala, ventromedial hypothalamus, septum, nucleus accumbens, and brainstem.

Sexual arousal: Oxytocin injected into the cerebrospinal fluid causes spontaneous erections in rats,[54] reflecting actions in the hypothalamus and spinal cord. Centrally administrated oxytocin

receptor antagonists can prevent noncontact erections, which is a measure of sexual arousal.

Studies using oxytocin antagonists in female rats provide data that oxytocin increases lordosis
[62]

behavior, indicating an increase in sexual receptivity.

Bonding: In the prairie vole, oxytocin released into the brain of the female during sexual activity is

important for forming a monogamous pair bond with her sexual partner. Vasopressin appears to
[63]

have a similar effect in males.

Oxytocin has a role in social behaviors in many species, so it

likely also does in humans. In a 2003 study, both humans and dog oxytocin levels in the blood

rose after five to 24 minutes of a petting session. This possibly plays a role in the emotional bonding between humans and dogs.[64]

Maternal behavior: Female rats given oxytocin antagonists after giving birth do not exhibit typical maternal behavior.[65] By contrast, virgin female sheep show maternal behavior toward foreign

lambs upon cerebrospinal fluid infusion of oxytocin, which they would not do
[66]

otherwise.

Oxytocin is involved in the initiation of maternal behavior, not its maintenance; for

example, it is higher in mothers after they interact with unfamiliar children rather than their own.[67]

Drug interactions: According to some studies in animals, oxytocin inhibits the development of

tolerance to various addictive drugs (opiates, cocaine, alcohol), and reduceswithdrawal symptoms.[68] MDMA (ecstasy) may increase feelings of love, empathy, and

connection to others by stimulating oxytocin activity via activation of serotonin 5-HT1A receptors, if initial studies in animals apply to humans.[69] The anxiolytic Buspar (buspirone) also appears to
[70][71]

produce some or all of its effect via 5-HT1A receptor-induced oxytocin stimulation.

Preparing fetal neurons for delivery: Crossing the placenta, maternal oxytocin reaches the fetal

brain and induces a switch in the action of neurotransmitter GABA from excitatory to inhibitory on

fetal cortical neurons. This silences the fetal brain for the period of delivery and reduces its vulnerability to hypoxic damage.[72]

Romantic attachment: In some studies, high levels of plasma oxytocin have been correlated with

romantic attachment. For example, if a couple is separated for a long period of time, anxiety can

increase due to the lack of physical affection. Oxytocin may aid romantically attached couples by decreasing their feelings of anxiety when they are separated.[27]

Drug forms

[edit]

Synthetic oxytocin is sold as proprietary medication under the trade names Pitocin and Syntocinon, and

as generic oxytocin. Oxytocin is destroyed in the gastrointestinal tract, so must be administered by

injection or as nasal spray. It has a half-life of typically about three minutes in the blood, and given intravenously does not enter the brain in significant quantities it is excluded from the brain by the bloodbrain barrier. Evidence in rhesus macaques indicates that administration of oxytocin by nasal
[73]

spray elevates oxytocin levels in the brain (e.g., ) but does not prove that it enters the brain, as opposed

to stimulating release from neurons within the brain via olfactory nerve stimulation, for example. Oxytocin
[74]

nasal sprays have been used to stimulate breastfeeding, but the efficacy of this approach is doubtful.

Injected oxytocin analogues are used for labor induction and to support labor in case of difficult parturition.

It has largely replaced ergometrine as the principal agent to increase uterine tone in acute postpartum

hemorrhage. Oxytocin is also used in veterinary medicine to facilitate birth and to stimulate milk release.

The tocolytic agent atosiban(Tractocile) acts as an antagonist of oxytocin receptors; this drug is registered

in many countries to suppress premature labor between 24 and 33 weeks of gestation. It has fewer side

effects than drugs previously used for this purpose (ritodrine, salbutamol, and terbutaline).

The trust-inducing property of oxytocin might help those who suffer from social anxieties and mood
[51] [75][76] [77]

disorders,

but with the potential for abuse with confidence tricks

and military applications.

Potential adverse reactions

[edit]
[78]

Oxytocin is relatively safe when used at recommended doses, and side effects are uncommon. following maternal events have been reported:[78]

The

Subarachnoid hemorrhage

Increased heart rate

Decreased blood pressure

Cardiac arrhythmia and premature ventricular contraction

Impaired uterine blood flow

Pelvic hematoma

Afibrinogenonemia, which can lead to hemorrhage and death

Anaphylaxis

Nausea and vomiting

Excessive dosage or long-term administration (over a period of 24 hours or longer) have been known to

result in tetanic uterine contractions, uterine rupture, postpartum hemorrhage, and water intoxication,

sometimes fatal.

Increased uterine motility has led to the following complications in the fetus/neonate:[78]

Decreased heart rate or heart rate decelerations

Cardiac arrhythmia

Brain damage

Seizures

Death

Synthesis, storage, and release

[edit]

Oxytocin/neurophysin I prepropeptide

Identifiers

Symbols

OXT; OT; OT-NPI; OXT-NPI

External IDs

OMIM: 167050 MGI: 97453 HomoloGene: 55494GeneCards: OXT Gene

[show] Gene Ontology

Orthologs

Species

Human

Mouse

Entrez

5020

18429

Ensembl

ENSG00000101405

ENSMUSG00000027301

UniProt

P01178

P35454

RefSeq (mRNA)

NM_000915

NM_011025

RefSeq (protein)

NP_000906

NP_035155

Location (UCSC)

Chr 20:

Chr 2:

3.05 3.05 Mb

130.58 130.58 Mb

PubMedsearch

[1]

[2]

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view

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The oxytocin peptide is synthesized as an inactive precursor protein from the OXT gene.[79][80][81] This precursor protein also includes the oxytocin carrier protein neurophysin I.[82] The inactive precursor protein

is progressively hydrolyzed into smaller fragments (one of which is neurophysin I) via a series of enzymes.

The last hydrolysis that releases the active oxytocin nonapeptide is catalyzed by peptidylglycine alphaamidating monooxygenase (PAM).[83]

The activity of the PAM enzyme system is dependent upon vitamin C (ascorbate), which is a necessary

vitamin cofactor. By chance, sodium ascorbate by itself was found to stimulate the production of oxytocin from ovarian tissue over a range of concentrations in a dose-dependent manner.[84] Many of the same

tissues (e.g. ovaries, testes, eyes, adrenals, placenta, thymus, pancreas) where PAM (and oxytocin by default) is found are also known to store higher concentrations of vitamin C.[85]

Neural sources

[edit]

In the hypothalamus, oxytocin is made in magnocellular neurosecretory cells of

the supraoptic and paraventricular nuclei, and is stored in Herring bodies at the axon terminals in the

posterior pituitary. It is then released into the blood from the posterior lobe(neurohypophysis) of

the pituitary gland. These axons (likely, but dendrites have not been ruled out) have collaterals that innervate oxytocin receptors in the nucleus accumbens.[61] The peripheral hormonal and behavioral brain

effects of oxytocin are thought to be coordinated through its common release through these collaterals.[61] Oxytocin is also made by some neurons in the paraventricular nucleus that project to other parts of the brain and to the spinal cord.[86] Depending on the species, oxytocin receptor-expressing cells

are located in other areas, including the amygdala and bed nucleus of the stria terminalis.

In the pituitary gland, oxytocin is packaged in large, dense-core vesicles, where it is bound to neurophysin

I as shown in the inset of the figure; neurophysin is a large peptide fragment of the larger

precursor protein molecule from which oxytocin is derived byenzymatic cleavage.

Secretion of oxytocin from the neurosecretory nerve endings is regulated by the electrical activity of the

oxytocin cells in the hypothalamus. These cells generate action potentials that propagate down axons to

the nerve endings in the pituitary; the endings contain large numbers of oxytocin-containing vesicles,

which are released by exocytosis when the nerve terminals are depolarised.

Non-neural sources

[edit]

Outside the brain, oxytocin-containing cells have been identified in several diverse tissues, including
[87][88] [89] [90] [91]

the corpus luteum,

[92]

the interstitial cells of Leydig,

[94]

the retina,

the adrenal medulla,

the

placenta,

the thymus

[93]

and the pancreas.

The finding of significant amounts of this classically

"neurohypophysial" hormone outside the central nervous system raises many questions regarding its

possible importance in these different tissues.

Female

[edit]

Oxytocin is synthesized by corpora lutea of several species, including ruminants and primates. Along with

estrogen, it is involved in inducing the endometrial synthesis ofprostaglandin F2 to cause regression of the

corpus luteum.

Male

[edit]

The Leydig cells in some species have also been shown to possess the biosynthetic machinery to

manufacture testicular oxytocin de novo, to be specific, in rats (which can synthesize vitamin C

endogenously), and in guinea pigs, which, like humans, require an exogenous source of vitamin C
[95]

(ascorbate) in their diets.

Evolution

[edit]

Virtually all vertebrates have an oxytocin-like nonapeptide hormone that supports reproductive functions

and a vasopressin-like nonapeptide hormone involved in water regulation. The two genes are usually

located close to each other (less than 15,000 bases apart) on the same chromosome, and are transcribed
[96]

in opposite directions (however, in fugu,

the homologs are further apart and transcribed in the same

direction).

The two genes are believed to result from a gene duplication event; the ancestral gene is estimated to be
[54]

about 500 million years old and is found in cyclostomata (modern members of the Agnatha).

Role of Oxytocin in Fear and Anxiety Response

[edit]

Oxytocin is typically remembered for the effect it has on prosocial behaviors, such as its role in facilitating trust and attachment between individuals. Consequently, oxytocin is often referred to as the love hormone".[97] However, oxytocin has a larger, and more complex role than solely enhancing prosocial

behaviors. Oxytocin also plays a role in enhancing fear and anxiety, which is often overlooked.

There is a consensus that oxytocin has a modulatory effect on fear and anxiety; that is, oxytocin does not directly elicit fear or anxiety.[98] There are two dominant theories explaining the role oxytocin plays in fear

and anxiety. One theory states that oxytocin increases approach/avoidance to certain social stimuli. The

second theory states that oxytocin increases the salience of certain social stimuli, causing the animal or human to pay closer attention to socially relevant stimuli.[99]

Individuals who receive an intranasal dose of oxytocin identify facial expressions of disgust faster than individuals who do not receive oxytocin.[99] Facial expressions of disgust are evolutionarily linked to the

idea of contagion. Thus, oxytocin increases the salience of cues that imply contamination, which leads to a

faster response because these cues are especially relevant for survival. In another study, after

administration of oxytocin, individuals displayed an enhanced ability to recognize expressions of fear

compared to the individuals who received the placebo.[100] Oxytocin modulates fear responses by

enhancing the maintenance of social memories. Rats that are genetically modified to have a surplus of

oxytocin receptors display a greater fear response to a previously conditioned stressor. Oxytocin

enhances the aversive social memory, leading the rat to display a greater fear response when the aversive stimulus is encountered again.[98]

Differential Role of Oxytocin in Male and Females

To make the role of oxytocin even more complex, it has been shown that oxytocin differentially affects

males and females. Females who are administered oxytocin are overall faster in responding to socially relevant stimuli than males who received oxytocin.[101][102] Additionally, after the administration of oxytocin,

females show increased amygdala activity in response to threatening scenes; however, males do not

show increased amygdala activation. This phenomenon can be explained by looking at the role of gonadal

hormones, specifically estrogen, which modulate the enhanced threat processing seen in females.

Estrogen has been shown to stimulate the release of oxytocin from thehypothalamus and promote receptor binding in the amygdala.[102]

Effect of Oxytocin in Predictable and Unpredictable Stimuli

Oxytocin increases defensive responding to unpredictable stimuli, but not to predictable stimuli. This result leads to the assumption that oxytocins effect is context-dependent. Thus, oxytocin may reinforce prosocial behaviors after an initial bond is formed, but may enhance defensive behaviors to unfamiliar individuals. [97]

Oxytocin is beneficial because it can either enhance social bonding or promote defensive behaviors depending on the situation.[97] It would not be adaptive if oxytocin consistently enhanced social approach

and other prosocial behaviors, especially in uncertain and potentially dangerous social contexts. Fear and

anxiety are typically thought to be maladaptive, as these traits often underlie various psychological

disorders. However, it is important to note that both fear and anxiety responses help to protect an

individual. These emotions render environmental cues more important, leading to a greater likelihood the

individual or animal will acknowledge the potential threat. Ultimately this process leads to a greater chance

of survival.

See also

[edit]

Carbetocin

Demoxytocin

Sexual motivation and hormones

Vasopressin

WAY-267,464

References

[edit]

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^ Jump up to:a b Theodoridou, Angeliki; Ian S. Penton-Voak, Angela C. Rowe, Angela Sirigu (ed.)

(2013-02-28). "A Direct Examination of the Effect of Intranasal Administration of Oxytocin on

Approach-Avoidance Motor Responses to Emotional Stimuli". PLoS ONE 8 (2):

e58113.doi:10.1371/journal.pone.0058113.

100.

Jump up^ Fischer-Shofty, M.; S.G. Shamay-Tsoory, H. Harari, Y. Levkovitz (January 2010). "The

effect of intranasal administration of oxytocin on fear recognition". Neuropsychologia 48(1): 179

184. doi:10.1016/j.neuropsychologia.2009.09.003.

101.

Jump up^ Theodoridou, Angeliki; Ian S. Penton-Voak, Angela C. Rowe, Angela Sirigu (ed.) (2013-

02-28). "A Direct Examination of the Effect of Intranasal Administration of Oxytocin on Approach-

Avoidance Motor Responses to Emotional Stimuli". PLoS ONE 8 (2):

e58113.doi:10.1371/journal.pone.005811.

102.

^ Jump up to:a b Lischke, Alexander; Matthias Gamer, Christoph Berger, Annette Grossmann,

Karlheinz Hauenstein, Markus Heinrichs, Sabine C. Herpertz, Gregor Domes (September

2012)."Oxytocin increases amygdala reactivity to threatening scenes in

females".Psychoneuroendocrinology 37 (9): 14311438. doi:10.1016/j.psyneuen.2012.01.011.

Further reading

[edit]

Lee HJ, Macbeth AH, Pagani JH, Young WS (June 2009). "Oxytocin: the Great Facilitator of Life". Progress

in Neurobiology 88 (2): 12751. doi:10.1016/j.pneurobio.2009.04.001.PMC 2689929. PMID 19482229.

Caldwell HK, Young WS III (2006). "Oxytocin and Vasopressin: Genetics and Behavioral Implications". In

Abel L, Lim R. Handbook of neurochemistry and molecular neurobiology. Berlin: Springer. pp. 573

607. ISBN 0-387-30348-0.

External links

[edit]

Hug the Monkey A weblog devoted entirely to oxytocin

Oxytocin.org 'I get a kick out of you: Scientists are finding that, after all, love really is down to a

chemical addiction between people', The Economist (February 12, 2004)

NewScientist.com 'Release of Oxytocin due to penetrative sex reduces stress and neurotic

tendencies', New Scientist (January 26, 2006) (paywall)

SMH.com.au 'To sniff at danger: Inhalable oxytocin could become a cure for social

fears', Boston Globe (January 12, 2006)

'Cuddle chemical' could treat mental illness (14 May 2008) New Scientist (paywall)

Molecular neurobiology of social bonding: Implications for autism spectrum disorders a lecture by

Prof. Larry Young, Jan. 4, 2010.

A TED talk by Prof.Paul Zak on Trust,Morality & Oxytocin

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Neuropeptidergics

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Peptides: neuropeptides

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Neurotransmitters

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Tocolytics/labor repressants (G02CA)

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