11.1 Oxytocin

What is oxytocin?

Classified as a hormone - released in the blood

What is oxytocin known as?

The love hormone

Oxytocin and parental care in humans

Experiments monitoring oxytocin levels and using fMRIs

What is the MPOA important for?

Expression of maternal behavior MPOA=part of hypothalamus

Female montane vole's preference

Female montane voles prefer to show no preference for the mate on the 1st day and actually prefer the stranger on the 7th and 14th days

What is pup retrieval?

If a mother rat is with babies on one side of the cage and one of the babies is moved to the other side, she will go and retrieve it and bring them back together

Drug that blocks function of oxytocin?

If a woman goes into premature labor - give her a drug that blocks function of oxytocin

What happens when oxytocin is increased?

Increases/induces uterine contractions

Social monogamy

Living with one other person, doesn't mean you are sexually monogamous

How is oxytocin made?

Made by neurons with cell bodies in the hypothalamus

What does oxytocin play an important role in?

Maternal and paternal behaviors and pair bonding or mating behaviors

*Results for oxytocin levels in parent interacting with offspring

-Mothers and fathers who scored high in affectionate or stimulatory contact=significant increase in oxytocin levels -Indication that interactions are giving positive feedback, after interaction they have higher levels of oxytocin - oxytocin activates brain regions involved in parental bonding and these parents are highly bonded with their babies -Mothers and fathers who scored low=decrease in oxytocin levels - less bonded with their babies

Monogamous relationships

-Not natural in our species -Different types -Only 3-10% of mammalian species are monogamous - most species, including humans, are socially but not sexually monogamous -Prairie voles are socially and sexually monogamous, but only one species

What about pair bonding in males and vasopressin

-Act of copulation induces the release of oxytocin in both males and females -In males, oxytocin is important for ejaculation and sperm release *In males, oxytocin is not required for pair bonding - but vasopressin is -The act of copulation will also increase the release of vasopressin in the male

Pair bonding - experiments done on rodents

-Affiliative behaviors - show that you have bonded with another individual: grooming, maintaining physical contact, remaining/getting in proximity, sexual behavior

Females

-After prairie voles have become familiar and copulated -act of copulation will induce release of oxytocin in female's brain and in male's brain -Oxytocin important in stimulating orgasm in female and sperm ejaculation on the male -Separated after becoming familiar -Female is put in neutral cage, could wander into other cage with unfamiliar male -Males tethered and can't leave cage -1, 7, or 14 days later -Amount of time female vole will spend in cage with her mate, in neutral cage alone, or in cage with stranger male -From day 1-14, female will spend much more time with familiar mate *Pair bonding has lasted a significant amount of time

Female rats show what maternal behaviors after giving birth?

-Arched back nursing -Licking/grooming -Pup retrieval

What happens when oxytocin is inhibited?

Reduces uterine contractions

*Inhibiting the function of vasopressin

-Either inject male with antagonist to vasopressin receptor (V1a) or inject with vehicle alone, CSF -Inject into a specific brain region called the lateral septum -Inject CSF - adult male prairie vole will prefer or have more contact time with his partner -After becoming familiar and mating, so the vasopressin would have been released, we block the vasopressin receptor with increasing amounts of the antagonist - see a decrease in preference for partner -At low levels of inhibitor, the males still prefer a partner, although a little bit less than they did when we did vehicle injections -By the time we get to 0.05 or 0.5 nanograms of antagonist, the male shows no preference for partner *We have to have vasopressin binding to receptors in lateral septum in order to trigger pair bonding in male prairie vole

Oxytocin and affiliation

-Feeling that we belong to a group - also leads to increased oxytocin

Affiliative behaviors?

-Grooming -Maintaining physical contact -Remaining/getting in proximity -Sexual behavior

Results

-In caudate putamen: just like injecting vehicle, female still prefers her partner -In nucleus accumbens: female prefers to spend time with stranger male - bored with male she spent 24 hours with -In prelimbic cortex: spends a lot of time with both stranger and partner *Oxytocin plays specific role in nucleus accumbens and prelimbic cortex *Role of oxytocin in nucleus accumbens is different than the role of oxytocin in prelimbic cortex

Parental care in rodents

-In many species, parental care is done entirely with females (distinctive behaviors)

Oxytocin effects in the body

-Induces uterine contractions -When baby gets into position and head presses on cervix, the stretching of muscles on the cervix causes a neural signal to go to hypothalamus that induces release of oxytocin -Oxytocin further stimulates uterine contractions -Cyclic phenomena

*What happens if you block oxytocin from having its function in the mother rat?

-Injected a drug called OTA which blocks oxytocin receptors - oxytocin is present, but it can't have any effect -In female rats at various time points after giving birth -Done at postpartum day 2,3 or 6,7 -Looking at 2 maternal behaviors - pup licking and arched back nursing -Look at change (0 means doing it just as much as before, negative number means decrease in behavior, positive number means increase in behavior) compared to before injection -Then inject either saline or oxytocin and monitor how much she did behaviors after

Blocking oxytocin results in rats

-Injecting oxytocin inhibitor=big effect in decreasing pup licking -Injecting oxytocin inhibitor=for day 2 and 3, not much effect on arched back nursing, but by day 6, 7 significant decrease in this behavior *Blocking oxytocin signaling will decrease important maternal behaviors (pup licking and arched back nursing)

*Study paired with previous study

-Looking at oxytocin levels and brain activity in fMRIs -Study done only on mothers -2 sessions -Session 1 - took oxytocin levels from mother's blood before or 5 minutes after interacting with baby -Session 2 - mother in fMRI shown pictures of their own baby or stranger baby, baby had happy, sad, or neutral facial expressions -Brain activity when seeing picture of your own baby vs. other baby -Session 1-positive number=increase in serum oxytocin levels-mothers have a bigger increase in oxytocin after playing with their babies -Session 2-greater activity in hypothalamus when mothers are seeing their own babies (also had more oxytocin released when interacting with their infant) *Tempting to say MPOA is activated since this is where oxytocin levels are associated with maternal and pup interactions in rats

Where does oxytocin act in the brain to facilitate pair bonding?

-Made in hypothalamus and released in pituitary and circulates throughout blood, but isn't actually binding to any receptors in pituitary -2 different species of prairie voles -Montane vole is not monogamous - after mating, show no preference for their partner -Vs. prairie vole - has dark staining (binding of receptors) much higher in 2 brain regions in prairie vole Prelimbic cortex (PL) Nucleus accumbens *A lot more oxytocin receptors in nucleus accumbens or prairie vole -Oxytocin might be binding in receptors in nucleus accumbens in order to be involved in behaviors of prairie voles

Pair bonding in male

-Male and female prairie vole in cage for 24 hours to familiarize themselves -But prevent them from copulation - no release of vasopressin -Amount of time spent in physical contact -After 24 hours together without mating, male will have preference for his partner, though not as much as if they had mated -Inject vasopressin (AVP) - *the more vasopressin injected into the male prairie vole, the more preference he will show for partner *Vasopressin alone can cause increase in preference for the partner in the absence of actually mating -No mating=no increase in oxytocin levels

Oxytocin and pair bond formation in females

-Mating behavior has caused oxytocin to be released in female and male's brains -Inject oxytocin receptor blocker into female's brain - called OTA -OTA circulates throughout body and brain -2 controls - inject vehicle (CSF, solution drug is dissolved in) or inject vasopressin receptor inhibitor -Inject vehicle - female spends most of time with familiar mate -Oxytocin inhibitor - female now spends equal time between mate and stranger -Inhibit vasopressin rejecter - still has preference for familiar male, this tells us the specific change in oxytocin causes female to spend equal time *Blocking oxytocin receptor can block mating preference

*Where in the brain is oxytocin exerting these effects?

-Medial preoptic area - directly above optic chiasm, but has nothing to do with vision -Saline or oxytocin inhibitor injected -Lactation days 1 through 5 and amount of time spent doing behavior per hour -Inhibit oxytocin receptor and see an immediate effect on arched back nursing for day 1-5 -Time mother spent with/on top of pups didn't decrease until 2nd or 4th day *Immediately blocking oxytocin receptors decreased total amount of time mother spent in the arched back nursing posture *Causative role

Can oxytocin make non-binding voles form pair bonds?

-Montane voles not monogamous sexually or socially -With female prairie vole, there are high levels of oxytocin receptor expression in nucleus accumbens -Nucleus accumbens oxytocin levels directly correlate with pair bonding *Could we cheat a montane vole into a monogamous relationship by putting more oxytocin receptors into the nucleus accumbens?

Try to induce a mating preference?

-Only keep virgin rats together for 6 hours -Reduce female's preference of male - only prefer familiar male 50% of time rather than 80% -Less time to get to know each other=only prefers male about 50% of time -Inject oxytocin or vasopressin into her brain -Vasopressin slightly increases how much time she'll spend with her partner -Oxytocin causes even greater increase in time with partner *Injecting with oxytocin makes it so female will spend as much time with her partner as if they were together for 24 hours *Increasing oxytocin increases preference for partner

How are oxytocin and vasopressin related?

-Oxytocin and related hormone vasopressin both made by hypothalamic neurons -These neurons send their axons into pituitary gland *Oxytocin and vasopressin both released in pituitary

Historical perspective

-Oxytocin first discovered by Henry Dale - early 1900s -Dissected out the posterior pituitary gland from an oxen and purified an extract from the gland -Used an oxen because of its large pituitary gland (and used as farm animals - relatively available) *The purified extract induced contractions in uterus of guinea pigs and other mammals -When extract is injected - sudden increase in force that remains constant and high for extended period of time

*Testing pair bonding in the lab

-Specialized type of cage - 3 cages linked together by tunnels - able to open and close doors connecting tunnels -Familiar, neutral, and unfamiliar cage -Male and female prairie voles in cage together, have to stay in cage together for 6-24 hours and get to know each other -At this point, they are familiar with each other -Test out how much they are bonded - do they prefer each other?

*Oxytocin and maternal behavior in virgin rats

-Took rat pups and put them in cage with virgin female -Scored her behavior in 5 categories - licking, grooming, arched back, nest building, retrieval -Normally if virgin female is injected with saline, she did none of the behaviors -Same with vasopressin - didn't do any behaviors -If injected with oxytocin - increase in time spent doing behaviors *Causative experiment

Using a virus

-Use a virus which can induce the gene for the oxytocin receptor to be expressed in the nucleus accumbens -In image B, after we have increased the oxytocin receptor, we see a lot of binding indicating a lot of oxytocin receptor expression -Looking at how much time the female prairie vole will spend in close proximity to one partner vs. a stranger -In control labeled GRP or in animals where we have increased expression of the oxytocin receptor *Female has no preference for partner vs. stranger and we do not change that by increasing the receptor expression *Just increasing oxytocin receptor expression alone is not enough to change montane vole into a monogamous vole

Effects of oxytocin receptor blockade in specific brain areas

-Virgin male and female prairie voles together for 24 hours, mate and cohabitate -Then block oxytocin receptors - inject OTA into nucleus accumbens, prelimbic cortex, or control area of caudate putamen -Inject cerebral spinal fluid as a control -For another control, inject vehicle alone -Inhibitor injected before virgin animals are put together CSF control group - female will spend a lot more time with partner when she's put in test chamber with him

Milk letdown reflex

-When baby begins to suckle at nipples, this triggers oxytocin release into bloodstream -Oxytocin travels back to breast tissues and induces release of milk by activating myoepithelial cells -Oxytocin stimulates milk release

What does Pitocin do?

-Woman late to go into labor - give her a hormone called pitocin which will induce uterine contractions -Pitocin is synthetic form of oxytocin

Sexual monogamous

Sex with only one person, could live with multiple people

*Oxytocin levels in parents interacting with offspring

Parents told to play with baby for 15 minutes - play and touch interaction period -Babies between 4-6 months in age -Observer scored parents according to how often and manner in which they interacted with babies -Affectionate contact=cradling baby -Stimulating contact=doing things to engage baby in play -Mothers spent more time in affectionate behavior, fathers spent more time in stimulating behavior -Monitored oxytocin levels in saliva before interacting with babies and after -Mothers scored as high or low affectionate contact - low score could mean mother spent high amount of time doing stimulatory play -Fathers scored as high or low stimulatory play -Oxytocin levels before and after 15 minute play touch session

What is arched back nursing?

Phenomenon exclusive to animals with large liters -Mother rat arches back over pile of babies -Babies have access to nipples for nursing and prevents suffocation of babies

Pituitary connections?

Pituitary has lots of vascular connections - things released into pituitary can travel through bloodstream and travel anywhere in body

Where are oxytocin and vasopressin released?

Posterior lobe of pituitary gland

Where are oxytocin and vasopressin produced?

Produced by neurons in the hypothalamus

Oxytocin and parental care (what about oxytocin in the brain?)

Role in interaction between parents and babies -Important because babies are born unable to take care of themselves -Babies need nourishment, shelter, warmth, protection -Parental care also has a big influence babies' brain development -Physiological and behavioral development influenced *Oxytocin stimulates this parental care

Difference between oxytocin and vasopressin?

Vasopressin and oxytocin are made by different types of neurons, but both types of neurons are in hypothalamus

Virgin rats ignore/avoid pups?

Virgin female rats will avoid pups for a certain amount of time, but after she's been with them for an extended period (several days) she may begin to display some of these behaviors -like licking/grooming and pup retrieval (not arched back nursing)