Lecture 15 - Oxytocin

Question 1

Attachment is critical for humans

Answer 1

Parental attachment
Partner attachment
Trust

Key for our development and happiness
Evolved to allow for survival and propagation of species
Co-opted for more nuanced attachments

Question 2

Oxytocin basics

Answer 2

Oxytocin is a hormone
Neuropeptide in PVN and SON (Supra orbital nucleus)
Direct projection to posterior pituitary

Oxytocin released increases through pregnancy
Fetal DHEAS from adrenals
Thinning cervix and contractions

PVN and SON fire in unison: cause pulses of oxytocin to start labour and then positive feedback loops that go in

Stimulates prolactin release

oxyticin projects to VTA Nac and PFC important for motivated behaviour and perceptions of what is rewarding, projections to the amygdala suggest modifications of emotional responses and Hippocampus suggests role in memory

Question 3

Projections of oxytocin center

Answer 3

Post pit
Olfactory bulb
Medial Preoptic Area
Amygdala
Hippocampus
Limbic System

Question 4

Oxytocin initiates labour

+ve feedback via prostaglandins

Answer 4

Oxytocin is increased in all placental mammals at labour
Enhanced by increased receptors

(a) Estrogen increases oxytocin receptors on the uterus
(b) Oxytocin is released from mothers and fetus pituitary
(c) this 1 - stimulated the uterus to contract and 2 - stimulates the placenta to make prostaglandins

Prostaglandins both reinforce uterus contraction and feedback positively to make more oxytocin

So it is a positive feedback loop

Ramps up to the point of birth

Synthetic oxytocin: Pitocin/Synotocin
Labour induction in 25% women

Question 5

After labour, what to OT do?

Answer 5

Development of Maternal Behavior

Virgin/non-maternal rats cannibalize babies

Intracerebral oxytocin + E2
Maternal behaviour in virgin female rats
MPOA or VTA
Antagonism OT blocks maternal behaviour

True in sheep too
Farmers induce fostering

OT wont cros the BBB so you need to put it in the spine to have these effects

Question 6

Auditory cues and maternal behavior

Answer 6

Ultrasonic call of pup
Activate auditory cortex
OT receptors
Makes them more responsive

OT release at birth stimulates these receptors
More responsive to pup cry
Make virgins react to pup cry with OT to the auditory cortex
Makes pups more likley to live

OT stimulates auditory and olfactory processing of pup cues
Drives start of maternal behaviour

Question 7

Oxytocin initiates lactation

Answer 7

Oxytocin at labour: initial push for lactation

Physical stimulation of nipples:

Oxytocin contracts mammary glands

Prolactin instigates milk production
(one is not enough)

Suckling also increases milk production while the infant feeds

Question 8

Lactation and maternal behaviour

Answer 8

Pups nuzzle mother’s ventral surface back arches and crouch over her pups.
Kyphosis
And checking pups are ok
Licking and grooming

Contact with ventral surface stimulates more OT
Important for maternal behavior and activation of MPOA, VTA and NAc
These are all important for reward learning which makes it more likely the mother will keep being a good mom

Learning of maternal behavior and bond

Question 9

Human Maternal Behaviour

Answer 9

Oxytocin is important for human labour
Used for induction

Oxytocin also stimulates mammary glands for nursing
Repeated behavior for (feeding from milk letdown)learning
Important for maternal bond?

Does oxytocin also affect maternal behavior in humans?

Question 10

Evidence for neuro basis of human affiliation

Answer 10

Examined oxytocin during pregnancy and 1 month postpartum

OT from blood samples

Interview with mother on parenting experience
Maternal preoccuopation, attachment representation, checking on infant etc

Videotaped a 15min interaction between mother and child

Blind coders using Feldman scale of attachment

Results

Variation in oxytocin and cort across pregnancy, found elevated levels in 1st trimester but highest in 3rd

Is this variation related to maternal behavior?

Negative correlation between oxytocin and cort

Positive correlation between oxytocin and maternal behavior
-Related to maternal preoccupation
-Related to attachment representation
-NOT related to checking behavior
(this is more anxiety)

Oxytocin is related to development of maternal behaviour

Question 11

Oxytocin and Paternal Care

Answer 11

What about Dad’s?
Oxytocin important for paternal bond?

Mothers and fathers interacting with their children
Scored as low or high affection by observing physical touching

Measured oxytocin in saliva following contact with children

Does oxytocin increase following in males interacting with offspring?

Oxytocin is not different at baseline for moms or dads BUT

Increase in oxytocin only in high affection parents

Role for oxytocin in maternal and paternal bond

Question 12

Gaze in Sexual Desire vs Romantic Love

Answer 12

Men and women looked at photographs to rapidly determine if they elicit:
romantic love in them
sexual desire in them

Tracked their eye movements to determine where they were looking to make their decision

No sex differences in eye movement

Fixate more often on face when see images determined to be romantic love

Face and eye contact important in romantic love

Question 13

Oxytocin increases gaze to eyes

Answer 13

Can administer oxytocin via intranasal spray
Leaps and bounds in research

If oxytocin and gaze are both important for bonding maybe oxytocin affects gaze
Intranasal oxytocin effects on gaze to human faces (photos)

Pictures shown for 2sec each

Decreases gaze to forehead and cheeks

Increases gaze to eye and mouth region in OT spray condition

Oxytocin playing an important role in bonding in general

Question 14

Oxytocin and development of maternal behaviour

Lamb fingering

Answer 14

Administer oxytocin to cause ewe to foster lamb

Vaginocervical causes ewe to foster lamb too
Genital stimulation = oxytocin
Nipple stimulation =oxytocin

back in the day before had synthetic oxytocin nfarmers could cause this with manual vaginocervical stimulation. Turns out this causes oxytocin release too, so see stim of primary and secondary sex organs cause oxytocin release. Get release of this hormone important in mother child bond.
Has implications for how sex will affect bonding – release of oxytocin in the presence of a sexual partner will drive the formation of a bond, particularly in women for whom oxytocin is more abundant than males. T^hat is what we are really looking at today – the role of oxytocin in romantic relationships. Goint to do that using a lot of research from a new type of rodent, the vole!!

Question 15

Oxytocin in developing a Pair Bond

Answer 15

Stimulation of breasts and vagina during sex can cause release of oxytocin

Oxytocin release during sex might initiate romantic bond

Question 16

Monogamy in animals

Answer 16

Socially monogamous

Will still bang around

Question 17

Bonding in Voles

Answer 17

So how is a Prairie vole different from a Montane vole?

Hormonal differences responsible for differing behavior
Oxytocin?

SO prarie voles form monogamous family units, at least some of the time, while mountain voles do not. Lets take a bit more time to go through the reason these sub-species are thought to be distinct
Lower maternal care in single parent units lead to the cvole equivalent of low licking and grooming in rats. See longterm effects on parenting behaviour, but also on future pair bonding….suggests a similar mechanism for maternal and partner bonds

Oxytocin released during sex
Male and female

Oxytocin manipulation on sex and bonding more effective in Prarie Voles

Difference in oxytocin receptor distribution
Higher in the NAc, PFC, and hypothalamus

Same amount of oxytocin has greater effect

So there is the same amount of OT release (and endorphin, but not topic today. However OT has much larger effect on mating and parental behaviour in prarie – if same OT levels HOW???

Receptor distribution – touched on this last class, but central today – distributin of receptors key. Same amount of hormone but way more recptors for binding means that hormone can have a greater effect. Exactly what Young and others figured out. Although OT levels the same, the difference in receptors, with waaaay more in Prarie voles, suggested that this hormone has greater effect

There is much more OT receptors in the prarie vole than the montane one and in their nucleus accumbens (involved in reinforcement learning) so social learning is being reinforced

Question 18

Increasing OT receptors in voles

Answer 18

Working Hypothesis:
Prairie voles are more parental and form pair bond because they have more oxytocin receptors

Does increasing oxytocin receptors (OXTR) in Prairie voles increase parenting behavior and pair bonding?

Adeno-associated viral vector: overexpress OXTR
Examine parental behavior and partner preference 2 months later

SET UP

Juvenile female Prairie voles

Adeno-associated viral vector (AAV) gene transfer
Over express OXTR during puberty

DNA viruses use cells DNA and RNA machinery to reproduce themselves
Insert gene into virus and virus into Prairie vole nucleus accumbens
Increase production of gene of interest (OXTR)

Test alloparental behavior and partner preference ~2 months later
Longterm effects of elevated OXT receptors

RESULTS
Note that these were nulliparous voles, meaning they had not had a litter of pups themselves. When they were testing response to pups they used pups from another mother. Thus Prarie voles would be expected to show some care, but relatively low since not their own offspring and had not gone through the pregnancy and birth process that we now know helps to foster a bond and care behavior via hormones.

GFP is a visal tag put onto the virus so you can see what brain areas it actually affected. This is essentially a control group – got the same tag for visualization but no change in DNA sequence to produce oxytocin receptors
Soo have a group with no brain injection (Sham), we have one with this injection but no virus to alter OTR, we have a group where he was aiming for the Nac but hit a different region, and finally, we have the group with elevated OTR because of this virus.

Increase lick and groom pups only with increased OXTR in Nac, so increased parental behaviour, good start but looked at other behaviours too.

Partner Preference Test
Female and male together for either 6 hours
NOT normally long enough to form pair

Separated for 30min before preference test

Time spent immobile with both voles

Typically need at least 12 hours together for a strong bond to form, so in theory these females should not be bonded yet. Wanted to test if the increase in OTR could increase

Increased time spent with partner after only with increased OXTR in NAc

Question 19

Oxytocin in the NAc

Answer 19

Critical for formation of bonds
Parental and partner

Individual differences in prairie voles based on OXTR in NAc

Done with Montagne voles too = behave more like prarie voles

Question 20

Do humans behave like voles?

Answer 20

In voles: parental behaviour from increased action of oxytocin and vasopressin
Visual, tactile, olfactory cues from pups stimulate hormone release

Pair bonds between adults based on higher activation of oxytocin and vasopressin systems

In humans: both men and women, oxytocin levels rise dramatically during offspring care giving and romantic interactions
Visual, tactile and olfactory stimulation can have these effects

The human brain manufactures and uses vasopressin and oxytocin in much the same way
Maternal behavior in an expectant mother arises from hormonal changes that her system induces, and after birth it usually stems from hormones her offspring stimulates. Breast feeding causes some of the stimulation.

Vasopressin enters the bloodstream during sexual arousal, and oxytocin at orgasm (Carmichael, et al. 1994; Insel, Carter 1995). In both female and male humans, oxytocin levels rise dramatically during sex, and may promote the associated feelings of love and infatuation. A simple touch can release oxytocin. Humans share many of the oxytocin and vasopressin responses of animals.

Question 21

Oxytocin in human pair bonds

Answer 21

Difficult to study –when will a human pair bond will start??
Research on associated emotions/behaviours

Intranasal oxytocin administration:
Decreases hormonal and psychological stress response
Increases eye gaze and trust (game theory)
Increases ability to read others emotions

Suggest oxytocin might facilitate healthy relationships

STUDY
Intranasal oxytocin
administered to both members of a couple
Discuss a “conflict issue” for 10min

Measure stress hormones and interaction during conflict

Oxytocin increase positive:negative interactions

Oxytocin resulted in decrease in stress hormone cortisol
Greater effect on women’s cortisol

Question 22

Sex differences in oxytocin function: role in sexual orientation

Answer 22

Oxytocin plays greater role in female pair bonding than in males
Organized early in life like other sex difference in hormones (e.g. LH)

Differences in hetero and homo -sexual male response to oxytocin?
Reduced early life androgens hypothesized to contribute to homosexual orientation
“Feminized” response to oxytocin?

STUDY

Intranasal administration of oxytocin to hetero and homo –sexual men
Happy, neutral and angry faces rated
Oxytocin in women increases perception of faces as trustworthy

Suggests that oxytocin has greater effect in homosexual men than hetero, similar to the difference seen btween men and women

Question 23

Oxytocin in human pair bonds

Summary

Answer 23

Associated with behaviours that support healthy relationships
Increased empathy, trust, and eye contact
Reduced stress

Increasing oxytocin increases positive:negative interactions in couples

Role in committed human relationships

Greater role in females

Gonadal hormone organization and activation contribute to sex differences in oxytocin

Oxytocin effects differ between hetero and homo -sexual males

Support of biological basis for homosexuality

Question 24

Oxytocin increases bonding and trust…..

Answer 24

Oxytocin promotes social attachment and affiliation in animals
Also affect prosocial approach behaviors - such as trust?
Major marketing push for perfume/cologne

However, we may be overstepping in some of these assessments….

Question 25

The trust game

Answer 25

Investment tripled when invested, so if put in $4 then the trustee actually gets $12, etc…..

The trustee then determines how much to return, they could be kind and send back half because without the investors trust they would have nothing, or they could choose to keep all the money for themselves

Should be noted that each person was EITHER trustee or investor, not both, and each did this 4 times, but with a different partner, so only interacted with each person once.

Question 26

OT and the trust game

Answer 26

TRUST EXPERIMENT

highest tranfer much more commonly when the investor, who is the one using trust here, is administered oxytocin

RISK EXPERIMENT

• risk condition - you knew you were playing against a computer (non-human) so not trustworthy or empathetic, would randomly determine amount back

See no effect here, so oxytocin not causing random blind faith or financial irresponsibility or impulsivity. Here see $8 investment so keep some money while giving enough that the investment could be profitable.

HOWEVER!!

• didn’t work the other way around - the trustee was not giving back more

Affect the subjects approach to the situation, since trust is required by the investior. Not required by trustee because it is a one off….if game many rounds, trustee would need to be altruistic/generous too but not the case. Thus, trustee no need to inspire trust in others, so gives back reasonable amount but not half

First hint that the oxytocin story is not entirely what it seems

Of course, this finding could be misused to induce trusting behaviours that selfish actors subsequently exploit. However, our findings may also have positive clinical implications for patients with mental disorders that are associated with social dysfunctions (for example, social phobia or autism).

Evidence that OXYTOCIN MIGHT MAKE ONE MORE TRUSTING WHEN DEALING WITH A HUMAN BUT NOT MORE PROSOCIAL NOT TRUSTING OF A NON-HUMAN

Question 27

Autism: a deficit in social interaction

Answer 27

More common in males
Deficits in eye contact, social cognition, empathy, bonding
Role for oxytocin?

Could alterations in oxytocin or vasopressin receptors contribute to this disorder?

Could symptoms be reduced with vasopressin/oxytocin?

Question 28

Autism is linked to reduced oxtytocin

Answer 28

Oxytocin levels lower in plasma of Autistic individuals

Intranasal oxytocin decreases repetitive behaviours

Intranasal oxytocin improves non-verbal processing of others emotions
(sig improvement in ability to process things)

Question 29

Meta analysis on the effects of OT

Answer 29

Meta Analysis – are the effects of oxytocin consistent?
Spoiler alert – not at all
Trust and bonding complex – own desire, others emotion, their response, environmental context

Need to look at the context in which oxytocin elicits its effects
Interaction between contextual cues and the hormone

Oxytocin improves social recognition/competence
Only true when task is difficult or when people are bad at it

Oxytocin increases prosocial behaviours
Not true if other person unknown, untrustworthy, or a social outgroup

43% studies find no main effect of OT and 63% find OT is moderated by another variable in the experiment

Even evidence for antisocial behavior following oxytocin, with people forming us vs. them perceptions and increasing negativity towards people that are not a part of their in-group. Trust for some may be paralleled by a distrust for others who are not like us.

Why?

Question 30

Meta analysis on the effects of OT

Mechanism

Answer 30

Oxytocin reduces anxiety
Reduction in social anxiety could explain prosocial effects

See reduced amygdala activation to stressor with OT on board suggesting less anxiety and fear in response to stimuli

Oxytocin affects motivational state related to affiliation
More drive to make connections, so they will form IF others reciprocate

Oxytocin alters perceptual salience of cues
Increases in eye gaze mean you will notice social advances more readily

IF not reciprocated; Could get strong negative response if put self out there and not well received – has been linked to us vs them mentality too – forming affiliations with certain individuals leaves others out in the cold SO CAN INCREASE US/THEM