• Overview and Learning objectives
• Human maternal behaviour
• Child abuse
• Initiation of maternal behaviour at parturition
• Maternal behaviours
• Onset of maternal behaviour
• Hormone levels during pregnancy

• Hysterectomy and ovariectomy in the rat: what is involved?
• Maternal behaviour after hysterectomy
• Maternal behaviour after hysterectomy + ovariectomy
• Effect of estrogen on maternal behaviour after hysterectomy + ovariectomy
• Summary table:Effect of hormones on maternal behaviour
• Oxytocin elicits rapid onset of maternal behaviour

• Maternal behaviour declines after pup removal
• Pup contact establishes maternal behaviour
• References
• Supplementary material
• Feedback

Overview
This lecture may not be of immediate personal concern to some of you, but hopefully you will all at some time experience the joys of parenthood. This is how my personal interest in the topic arose.

When my son was born I began to wonder how the interaction between mother and child was controlled. And this set off a research programme concerned with factors that control the defining mammalian behavioural pattern - suckling.

The lecture begins with a look at the psychological changes that occur during human pregnancy. I draw your attention to this material because it seems to me that this area provides a rich resource of research questions that could be tackled in a third year project.

But in order to understand the biology of parenting we need to resort to an animal model, and once again the humble lab rat comes to the rescue. In fact, maternal behaviour in the rat is remarkably robust and reliable. By this I mean that it is really very easy to observe these behaviours under laboratory conditions. We look at two behaviours, retrieving and suckling, that can be elicited very easily. How unlike some of the behaviours that we try to study in the lab!

We then move on to ask questions about the role of hormones in the initiation of maternal behaviours. Three candidates - estrogen, progesterone and prolactin - have received extensive investigation by Jay Rosenblatt and his co-workers in an elegant series of experiments. Although these studies suggest that maternal behaviour is facilitated by a decline in progesterone, and an increase in estrogen levels, they do not account for the rapid onset of maternal behaviour immediately after parturition.

Recent work with central injection of oxytocin is described to illustrate how this research field is still revealing answers.

Finally we will look at factors that control the maintenance of maternal behaviours in order to answer the questions "Do pups maintain maternal behavior by promoting the release of hormones in their mother?" or "Do pups simply provide a particular type of sensory stimulation?"

• Describe the changes in maternal engrossment and self-image that occur during pregnancy
• Describe a woman's feelings towards themselves, their partner, and their baby at various stages of pregnancy and after the birth of their child.
• Describe the change in olfactory recognition that occurs after birth
• List five maternal behaviours exhibited by rodents
• Recognise the terms: parturition, prepartum, and postpartum
• Describe the frequency of maternal behaviour in the rat before, and after, parturition.
• Describe the changes in progesterone, estrogen, and prolactin during pregnancy in the rat
• Explain the terms hysterectomy and ovariectomy and recognise the organs that are removed by these operations
• Describe the effects of hysterectomy during pregnancy on progesterone level and maternal behaviour in the rat
• Explain how, and describe the underlying rationale of, Rosenblatt's studies on the role of estrogen in the initiation of maternal behaviour
• Describe how the balance between estrogen and progesterone may affect the initiation of maternal behaviour
• Evaluate the extent to which we have a complete understanding of the role of hormonal factors in the initiation of maternal behaviour
• Describe the evidence which suggests that non-hormonal factors are responsible for maintaining maternal behaviour after birth

They computed the ratio of positive to negative statements given by the women in these semi-structured interviews.

Clearly these women doted on the new arrival to the family, but there is a message for partners in the data. You may be seen in an increasingly poor light as pregnancy advances, but things will get back to normal as soon as the baby arrives - she will have an equal number of good and bad things to say about you!

One of the most surprising abilities of new mothers is their ability to recognize their child on the basis of smell. This diagram shows the percentage of women who successfully recognized the odour of their baby as a function of how long they had been exposed to their child (Kaitz,1987).

This section of the lecture will outline some of the hormonal factors that regulate maternal behavior in the rat.

Studies of maternal behaviour in rats have been concerned with

• understanding how the behaviour is 'switched on' or initiated at the end of pregnancy and
• how the behaviour is maintained during lactation.

Maternal behavior is thought to be influenced by hormonal conditions that exist during pregnancy but sensory stimuli provided by the offspring are also important in initiation and maintenance. The idea that maternal behavior is "switched on" and maintained by hormones and sensory factors and maintained by sensory stimulation is central to this lecture.

Maternal behaviour is an attractive behaviour to study because it consists of a number of clear-cut behaviours
that are easy to observe and record under laboratory conditions.

Maternal behavior in rats and mice consists of the following elements:

• retrieving
• nest building
• nursing
• licking pups
• maternal aggression

In this photograph the dam is shown on her back suckling pups. Normally mothers crouch over pups in the 'nursing posture'. This picture shows an anaesthetized mother, and was taken during a research programme into the role of sensory cues in suckling behaviour .

The diagram shows the emergence of three maternal behaviours in the rat before, and after, parturition.

Notice that maternal behaviour is virtually absent during pregnancy but appear suddenly at parturition.

What is responsible for the rapid initiation of maternal behaviour postpartum?

One possibility - quickly disproved - was that the birth of the pups (through the birth canal) was responsible for the onset of maternal behaviour . In fact, delivering pups via Caesarean section does not disrupt the rapid onset of maternal behaviour.

Explanation of terms:

• parturition = birth
• prepartum = the period before birth
• postpartum = the period after birth

Notice that::

• progesterone declines during the last days of pregnancy
• estrogen increases just before birth
• prolactin increases just before birth

Is this cluster of hormonal changes responsible for switching on maternal behavior ? It is difficult to study the role of hormones in natural pregnancy because if you inject or remove hormones during pregnancy there are multiple effects on lactation and behavior that are difficult to disentangle.

• uterus
• ovaries
• foetus (unborn pup)

In mammals the fertilied egg passes through several stages before birth:

• in humans: embryo, foetus, baby
• in rats: embryo, foetus, pup

Rats normally give birth to large families of pups! A pregnant uterus can contain 16 or more unborn pups.

This diagram shows falling progesterone level in intact pregnant rats, and rats that were hysterectomised (H) on day 10, 13, 16 or 19 of their pregnancy

This diagram shows the cumulative percentage of females showing maternal behaviour following hysterectomy (H) on day 10, 13, 16 or 19 of pregnancy . The first test (0) of maternal behaviour was given 48 hours after surgery, and testing continued for a further 5 days.

Notice how hysterectomy and parturition are both associated with a decline in progesterone and an increase in maternal behavior .

The next question is: 'Are these changes causally linked?' Does the decline in progesterone trigger the onset of maternal behavior, or does the effect depend on some other effect of the operation?

This diagram shows the median latencies to the onset of maternal behaviour in pregnant rats that were hysterectomised (H) or hysterectomised + ovariectomised (HO) on days 10, 13, 16 or 19 of their pregnancy. The first test of maternal behaviour was given at 48 hours after surgery.

Results:

At each stage of pregnancy, ovariectomy reduces the effect of hysterectomy. Rats that are given the double operation (ovariectomy + hysterectomy) take longer to develop maternal behaviours than animals only given an hysterectomy.

This result suggests that it is the presence of high estrogen levels against a background of low progesterone levels that stimulates maternal behaviour at the end of a normal pregnancy. Rosenblatt went on to check this explanation by replacing estrogen in rats that had been ovariectomised by injecting them with estrogen.

• hysterectomised - progesterone declines, normal estrogen level
• hysterectomised + ovariectomised - progesterone declines, source of estrogen removed
• hysterectomised + ovariectomised + estrogen injection - progesterone declines, source of estrogen removed and then replaced with estrogen injection

The diagram shows the cumulative percentage of 10 day pregnant rats exhibiting maternal behaviour after hysterectomy or hysterectome-ovariectomy plus estradiol benzoate treatment (100 or 200 microgram/kg). Maternal behaviour tests began 48 hours after surgery and hormone injection.

Results:

• Ovariectomised rats take longer to exhibit maternal behaviour than hysterectomised rats.
• Injection of estrogen overcomes the effect of ovariectomy and restores the rapid onset of maternal behaviour seen in hysterectomised rats.

This result suggests that estrogen stimulates maternal behavior when progesterone levels are low. Recall that estrogen rises and progesterone declines at the end of a normal pregnancy.

However estrogen stimulates prolactin release so these effects may involve prolactin which increases dramatically around birth. This explanation is thought unlikely because blocking the release of prolactin with ergocornine or apomorphine does not interfere with the ability of estrogen to stimulate maternal behaviour. Consequently, the initiation of maternal behavior is probably caused by estrogen.

Estradiol up

Estradiol  down

Prolactin down

Beyond "the Blues": Postpartum Reactivity and the Biology of Attachment Most literature on postpartum psychiatric disorders accepts the premise that there are three general categories of postpartum disturbance, along a spectrum of increasing severity: "blues," depression, and psychosis.1-3 The most benign and most common condition is postpartum blues, experienced by approximately 50% of women who give birth. The blues are usually characterized as a mild, self-limited form of depression. There is a growing body of evidence to suggest that the term postpartum blues is a misnomer. This article reviews data supporting the idea that the blues are experientially and biologically distinct from depression . Rather, they are a normal state of psychophysiologic reactivity that facilitates attachment and maternal behavior. Reconceptualizing the blues this way should change the focus of research from variables relevant to depression to variables relevant to attachment. It may also foster a greater clinical understanding of attachment and disorders of attachment.

Impact on babies of mothers ingesting 'crack' cocaine They are called "a biological underclass" and "a lost generation." Those are just two of the milder name tags attached to the children we have come to believe were permanently damaged by their mothers' use of cocaine. The poster in maternity clinics conjure up the same image of the prenatally doomed: "Some people who smoke crack never get over it." The schools too have been put on emergency alert: "The crack babies are coming, the crack babies are coming." Indeed, the phrases "crack babies" and "crack kids" are shorthand for monster-children who are born addicted. These are the kids destined to grow up without the ability to pay attention or to learn or to love. But just when the name has stuck, it turns out that "crack baby" may be a creature of the imagination as much as medicine, a syndrome seen in the media more often than medicine.
Here is another link to similar material about the controversy surrounding the impact of cocaine on the unborn

A study of rat brains may offer hope to women who reject their babies. Published in New Scientist 13/12/97
"Mothers who feel no attachment to their newborn babies may lack a neural pathway that is normally triggered by the act of giving birth, a new study of mice suggests. The maternal skills of female mice genetically predisposed to neglect their young improve for good if they receive a burst of key neural chemicals shortly before giving birth, say researchers in Seattle. And while the factors that cause some women to reject their babies at birth remain unclear, the study hints that a carefully timed dose of drugs might, in some cases, free them from this misery. " more .....
Thanks to Bernadette Melmore (year 2, 1997) for pointing out this article.

The Daily Mail (30th April, 1998) announced it as a "PMT Breakthrough" and explained that "Pre-menstrual syndrome and postnatal depression are closely related to the 'cold turkey' experienced by addicts trying to give up drugs ..". Here is the description of the research given in Nature.

GABA receptor a4 subunit suppression prevents withdrawal properties of an endogenous steroid. Nature 392, 926 (1998)

"The hormone progesterone is readily converted to 3a-OH-5a-pregnan-20-one (3a,5a-THP) in the brains of males and females. In the brain, 3a,5a-THP acts like a sedative, decreasing anxiety and reducing seizure activity, by enhancing the function of GABA (g-aminobutyric acid), the brains major inhibitory neurotransmitter. Symptoms of premenstrual syndrome (PMS), such as anxiety and seizure, susceptibility, are associated with sharp declines in circulating levels of progesterone and, consequently, of levels of 3a,5a-THP in the brain. Abrupt discontinuation of use of sedatives such as benzodiazepines and ethanol can also produce PMS-like withdrawal symptoms. Here the authors report a progesterone-withdrawal paradigm, designed to mimic PMS and post-partum syndrome in a rat model. In this model, withdrawal of progesterone leads to increased seizure susceptibility and insensitivity to benzodiazepine sedatives through an effect on gene transcription. Specifically, this effect was due to reduced levels of 3a,5a-THP which enhance transcription of the gene encoding the a4 subunit of the GABAA receptor. The authors also find that increased susceptibility to seizure after progesterone withdrawal is due to a sixfold decrease in the decay time for GABA currents and consequent decreased inhibitory function. Blockade of the 4 gene transcript prevents these withdrawal properties. PMS symptoms may therefore be attributable, in part, to alterations in expression of GABAA receptor subunits as a result of progesterone withdrawal. "

Reference: S S Smith, Q H Gong, F-C Hsu, R S Markowitz, J M H ffrench-Mullen & X Li, GABAA receptor a4 subunit suppression prevents withdrawal properties of an endogenous steroid. (Letter to Nature) Nature 392, 926 (1998)

Thanks to Bernadette Millmore (Yr2) for bringing my attention to this research.