Topic 15: Oxytocin and Vasopressin

Question 1

When was oxytocin discovered?

Answer 1

one of only two hormones released from the posterior pituitary

described in 1906 as a compound able to elicit uterine contraction

identified and synthesized in 1953

classic hormone roles in labor and lactation

Question 2

What is vasopressin?

Answer 2

also known as arginine vasopressin (AVP), antidiuretic hormone (ADH), or argipressin

functions principally as a vasoconstrictor and antidiuretic; modulates aquaporin (water channels) in kidney nephron increasing water resorption

important regulator of water, glucose, and salt homeostasis

Question 3

What is the expression and function of OXT and AVP?

Answer 3

oxytocin and vasopressin are expressed on two seperate prepropeptide genes, OXT and AVP

cleavage of the preproOXT/AVP polypeptides give rise to OXT and AVP and an additional carrier protein (~90 amino acids)

preproOXT yields neurophysin I
preproAVP yields neurophysin II

neurophysins function as carrier proteins for the peptide hormones, likely facilitating their distribution and extending the half-lives of OXT and AVP in systemic circulation

Question 4

What are neurohypophyseal peptide hormones?

Answer 4

OXT and AVP are synthesized in secretory neurons in the hypothalamus that project to the posterior pituitary

OXT and AVP are released into systemic circulation to the hypophyseal portal system

Question 5

What are the roles of oxytocin?

Answer 5

OXT stimulates uterine contraction during childbirth

OXT stimulates milk letdown in response to suckling in lactating mothers

binds to a single receptor: OXTR-Gq coupled receptor

proposed to play roles in various human behaviors

social bonding, trust, stress, sexual arousal, love, generosity, maternal behavior, feeding, fear, empathy, inter-group bonding, envy

autism spectrum disorders

Question 6

What are the roles of vasopressin?

Answer 6

AVP regulates homeostasis of glucose, water, and salts

modulates water resorption in kidney nephron

decreased AVP function causes diabetes insipidus

hypernatremia (high blood Na+)
polyuria (excess urine production)
polydipsia (excess thirst)

binds to 4 different receptors, two expressed in CNS: AVPR1A, B (Gq coupled receptors), AVPR2, 3 (expressed peripherally)

Question 7

Where are oxytocinergic neurons located in the brain?

Answer 7

oxytocinergic neurons project from the paraventricular nucleus of the hypothalamus to the forebrain and hindbrain

notable innervation of the amygdala, NAc & VTA, hippocampus

Question 8

What are oxytocin systems?

Answer 8

oxytocinergic neurons project from the paraventricular nucleus of the hypothalamus to the forebrain and hindbrain

OXT is released from synapses at axon terminals, from dendritic structures, at parasynaptic (adjacent) sites, or en passent (along the length of axons)

OXTR is expressed in numerus regions including the cortex, limbic system, hypothalamus, and brainstem

OXT and AVP have some affinity at reciprocal receptors, thus are implicated in many of the same behaviors

some early studies suggest AVP/OXT roles may be sexually dimorphic

Question 9

What are the microtine rodent oxytocin experiments?

Answer 9

microtine voles are commonly used in a lab setting to examine social behaviors, bonding, and investigating the underlying neurochemistry of social behavior

social behaviors can be measured by using simple tests such as partner preference - measuring time spent interacting with a bonded partner vs a stranger

prairie voles: preference for bonded partner
meadow voles: no preference

prairie voles have more oxytocin receptors

OXTR binding capacity correlates with social behavior (measured by partner preference tests)

Question 10

How is oxytocin involved in early life social interactions?

Answer 10

maternal care is associated with increased OXT function

maternal separation decreases the expression of OXT, particularly in female offspring

in humans early childhood neglect correlates with decreased OXT levels in urine, and adult women with a history of child abuse have decreased OXT in CSF

human infants with high parent-infant synchrony (i.e. enhanced capacity to respond to infant’s socio-affective signals) have increased OXT levels in saliva compared with low parent-infant synchrony

effects seem to be cross-generational: human parents with high parent-infant synchrony also show increased salivary OXT

Question 11

How does early social life affect adult social behaviors?

Answer 11

early social deprivation induces changes in social behaviors that persist into adulthood in animal models: impaired maternal care, increased/decreased aggression (species-specific)

female offspring of low-licking/grooming dams (rats) show earlier sexual receptivity

male offspring of low licking/grooming dams show increased dominant play-fighting behaviors

early social deprivation and enhancement lead to correlations in OXT system function and social behaviors: current studies are investigating causality in animal models

Question 12

What are the effects of the genetic manipulation of OXT?

Answer 12

OXT and OXT receptor knockout mice produce social deficits

decreased social memory: fail to recognize conspecifics in social recognition tests, normal sensory/olfactory function and non-social learning and memory

decreased isolation anxiety: decreased ultrasonic vocalizations after maternal separation of pups

social behaviors can be restored in OXT/R KO models by intracerebroventricular injection of OXT before but not after initial social exposure

suggests a role of OXT in encoding but not recall of social information

possible role in enhancing saliency of social information

Question 13

How is oxytocin involved in autism spectrum disorder?

Answer 13

OXT/OXTR KO mice reproduce many deficits associated with ASD

persistent deficits in social communication and interaction: social-emotional reciprocity, non-verbal communication, developing, maintaining, and understanding relationships

restricted and repetitive patterns of behavior: stereotyped or repetitive motor movements, inflexible adherence to routines, restricted and fixated interests, hyper or hypo reactivity to sensory input

Question 14

What is oxytocin pharamcology?

Answer 14

oxytocin IV is used clinically to induce labor: induces uterine contractions, IV administration has a half-life of ~3 minutes

oxytocin has been explored to induce or facilitate lactation

intranasal oxytocin has been used to investigate behavioral effects of OXT: intranasal administration can bypass the BBB and prolongs the bioavailability of OXT, intranasal OXT is psychoactive and effects last 2-4 hours

Question 15

How does intranasal OXT affect social behavior?

Answer 15

IN-OXT improves social function in autism and schizophrenia

increases gaze-fixing on faces
improves social recognition and cognition
improves affective recognition and retention of affective speech
some studies show decreases in repetitive behavior

limited evidence for role of OXT in heritable cases of autism

deletion of OXTR gene in some families
evidence for methylation differences in OXTR (epigenetics)

Question 16

How does intranasal OXT alter behavior in healthy controls?

Answer 16

IN-OXT increases social cognition in healthy controls: increased gaze fixation, increased socio-affective processing

IN-OXT decreases emotional processing: in fMRI studies, OXT groups show decreased activation of the amygdala while viewing frightful faces or threatening scenes

IN-OXT administration increased disclosure of emotional events when recalling autobiographical stories

using trust games such as risky-investment scenarios IN-OXT increased subjects ratings of “trustworthiness” and generally gave more “money” to trustworthy recipients

Question 17

How is oxytocin involved in love and sexuality in human models?

Answer 17

in human fMRI studies, photos of a loved one increase activity in OXTR-rich areas

OXT/AVP release prolonged to contribute to development of monogamous bond

human-dog interactions increase OXT levels in both parties

OXT-rich areas such as the paraventricular nucleus are active during orgasm (measured via fMRI)

IN-OXT administration increased self-reported satisfaction without affecting physiological aspects of sex

Question 18

How is oxytocin involved in love and sexuality in animal models?

Answer 18

in prairie voles, OXT released in the female vole during mating: AVP released in the males

OXT administration into CSF of male rats causes spontaneous erection

Question 19

How is oxytocin involved in social salience?

Answer 19

many facets of both pro- and anti-social behavior are enhanced by OXT administration

reports of increased envy and Schadenfreude after IN-OXT administration

IN-OXT may reinforce or exacerbate in-group/out-group differences

popular conception of OXT as a “love hormone” likely reflects bias towards pro-social studies in published research

Question 20

What is the stop-distance paradigm?

Answer 20

subjects (male volunteers) are placed into an encounter with an attractive female experimenter

distance was varied between the subject and experimenter until the subject reaches a comfortable distance (ideal distance)

administration of intranasal OXT (but not placebo) had a specific effect on subjects in a relationship

OXT/relationship group maintained an average distance that was 10-15 cm greater than OXT/single or PLC/relationship

suggest OXT may reinforce fidelity

Question 21

What is still not known about how oxytocin effects behavior?

Answer 21

most data report only correlations between OXT and behavior

unknown mechanisms of OXT entry into brain after IN administration: possible feed-forward mechanism that induces OXT release in the CNS

enhancing effects of IN_OXT may not reflect a direct role of OXT in behavior

most measurements of OXT in studies use peripheral levels - may differ from CNS levels: urine, saliva, blood, sometimes, CSF