Topic 15: Oxytocin and Vasopressin Flashcards
When was oxytocin discovered?
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
What is vasopressin?
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
What is the expression and function of OXT and AVP?
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
What are neurohypophyseal peptide hormones?
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
What are the roles of oxytocin?
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
What are the roles of vasopressin?
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)
Where are oxytocinergic neurons located in the brain?
oxytocinergic neurons project from the paraventricular nucleus of the hypothalamus to the forebrain and hindbrain
notable innervation of the amygdala, NAc & VTA, hippocampus
What are oxytocin systems?
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
What are the microtine rodent oxytocin experiments?
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)
How is oxytocin involved in early life social interactions?
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
How does early social life affect adult social behaviors?
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
What are the effects of the genetic manipulation of OXT?
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
How is oxytocin involved in autism spectrum disorder?
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
What is oxytocin pharamcology?
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
How does intranasal OXT affect social behavior?
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)
How does intranasal OXT alter behavior in healthy controls?
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
How is oxytocin involved in love and sexuality in human models?
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
How is oxytocin involved in love and sexuality in animal models?
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
How is oxytocin involved in social salience?
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
What is the stop-distance paradigm?
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
What is still not known about how oxytocin effects behavior?
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
