Anti-stress effects during lactation: the role of suckling and oxytocin.
An excerpt from Oxytocin: The Biological Guide to Motherhood by Kerstin Uvnäs-Moberg, MD, PhD.
Also by the author: The Hormone of Closeness.
Not only milk production and milk ejection are driven by the suckling stimulus, maternal physiology and behavior/psychology are also subjected to many changes during the lactation period in order to facilitate adaptation to motherhood. In the previous chapter, some maternal protective strategies were described that may create aggression or defense reactions in the mother, e.g., certain types of stress which are or may be perceived as threatening to the newborn. The mother may also overreact to some types of physical stress.
In contrast, maternal reactions to some types of stress are reduced and her basal stress levels are reduced. The reason for this is that the mother should focus her attention on the newborn and direct her energy towards milk production. Oxytocin released in response to suckling participates in the control of some of these adaptations. For example, oxytocin released from nerves projecting from the PVN [paraventricular nucleus] to areas involved in the control of autonomic nervous function and of the HPA axis [hypothalamic–pituitary–adrenal axis] in the brainstem area and in the hypothalamus are involved in these anti-stress effects. The following two chapters will be devoted to the role of suckling-related oxytocin release in the regulation of stress levels.
Anti-Stress Effects in Lactating Animals
Increasing the levels of calm and reducing stress levels and stress reactions during lactation may serve many functions. It may divert maternal interest from irrelevant stimuli in the environment, thereby helping the mother focus her attention on the offspring. It may serve an even more basic function. By being calm and avoiding unnecessary stress reactions or physical movement, energy is saved. In this way, more calories may be used for milk production and the caloric demands of the offspring are ensured. Reduction of unnecessary energy expenditure is also achieved by a decrease of some aspects of the activity of the HPA axis and the sympathetic nervous system, and thereby unnecessary heat production or catabolic processes. The expressions of these adaptations vary between species as they are linked to the reproductive style of the different species and to how and under what circumstances they live.
Some lactating animals have to stay still for varying periods of time when they are giving milk to their offspring. The suckling stimulus activates mechanisms related to calm in the mother, which “helps” the mother stay in her nest. In some species, milk ejection is related to decreased consciousness. Rat mothers exhibit a slow wave EEG [electroencephalogram] during suckling, and no milk can be ejected unless the mother is “partly unconscious” (Lincoln et al., 1980; Voloschin & Tramezzani, 1979). This is not the case in pigs or rabbits, probably because they have to be more watchful during milk letdown than rat mothers, who hide in a dark place while nursing (Neve, Paisley, & Summerlee, 1982; Poulain, Rodriguez, & Ellendorff, 1981).
Reduced Physical Activity
Some lactating animals reduce their physical activity and stay in the nest for long periods of times during lactation. By reducing physical activity during the lactation period, they focus on their offspring and save large amounts of calories that can be used for milk production and growth of the pups. When weaning, these animals leave their offspring and return to normal activities. For example, hamsters kept in a cage spend large amounts of their time running on a wheel. Lactating hamsters spend most of their time with their pups and avoid running on the wheel. As soon as they wean their offspring, they resume running on the wheel. The decreased motor activity during lactation is linked to decreased activity in dopaminergic neurons in the striatum.
Reduced Reactivity to Certain Types of Stress
In addition, the reactivity to certain types of stressors is reduced in lactating animals. Rat mothers exposed to unexpected noise or light react less to these stimuli than non-lactating rats. The importance of some stressors, which are not linked to the protection of the offspring are down regulated (Neumann, 2001, 2002). The calming and reduced reactivity to the stress-reducing effect of suckling has been described in previous chapters.
Reduced Activity in the Sympathetic Nervous System and the HPA Axis
Rats have lower blood pressure during lactation than during pregnancy or other periods of life. The lowering of blood pressure is driven by the suckling stimulus and is mediated by a decreased tone in the aspects of the sympathetic nervous system that controls blood pressure. Still, blood flow to the mammary glands is increased, illustrating the complex change in the function of the cardiovascular system during lactation.
In several mammalian species, such as rats and cows, cortisol levels are increased in response to suckling (Gorewit, Svennersten, Butler, & Uvnäs-Moberg, 1992). Cortisol is important for recruitment of energy for milk production and contributes to the stimulation of milk production.
In contrast, regular stroking of the abdominal area decreases both pulse rate and cortisol levels in cows, and in some species, suckling also decreases cortisol levels. Lowering of cortisol levels is linked to saving energy.
This complicated energy equation has been solved in sometimes opposing ways in different mammalian species, depending on how they live, how many pups they need to feed, and so forth. In some species, cortisol levels are higher than during other periods of life and in some they are lower. In both cases they represent adaptations to provide energy to the offspring in the best way.
Role of Suckling and Oxytocin in the Inhibition of the Sympathetic Nervous System and the HPA Axis During Lactation
The structure and function of the sympathetic nervous system and the HPA axis, and the inhibitory effects exerted by oxytocin on these systems, as well as how oxytocin is released in response to suckling, was described in great detail in previous chapters. A short summary of these mechanisms will be given below to allow understanding of the mechanisms behind the oxytocin-mediated anti-stress effects caused by suckling.
The Sympathetic Nervous System and the HPA Axis
The sympathetic nervous system and the HPA axis represent two individual aspects of the stress system. The neurogenic sympathetic nervous system induces very quick responses, whereas the endocrine HPA axis reacts more slowly. The mechanisms involved have been described in great detail in previous chapters and only a short summary will be given here.
The sympathetic nerves innervate and activate the function of the cardiovascular system, the lungs, and the gastrointestinal and genitourinary organs. Noradrenaline is the main transmitter substance in the sympathetic nervous system. The adrenal medulla, which produces adrenaline, is part of the sympathetic system.
Cortisol is secreted from the adrenal cortex and is of major importance for all reactions linked to activity and stress. It is released by adrenocorticotrophic hormone (ACTH) from the anterior pituitary and the secretion of ACTH is regulated by corticotrophin-releasing hormone (CRF), which is produced in parvocellular neurons in the paraventricular nucleus of the hypothalamus (PVN). The release of CRF is under inhibitory control from neurons in the hippocampus. The HPA axis is under inhibitory control by cortisol released from the adrenal cortex, as it inhibits the secretion of CRF and ACTH via feedback (inhibitory loops).
The activity of the sympathetic nervous system and the HPA axis is influenced from many brain regions. The noradrenergic fibers that originate in the locus coeruleus (LC) and which are activated in response to stress, play an important regulatory role in both systems. In addition, noxious or painful sensory stimuli may activate noradrenergic fibers in the nucleus tractus solitarius (NTS), which stimulate the activity of the HPA axis and the sympathetic nervous system.
Reciprocal Activation of Brainstem and Hypothalamic Stress Systems
The noradrenergic neurons from the LC and NTS exert a strong influence on the secretion of CRF from the hypothalamus and thereby the activity of the HPA axis. At the same time, CRF-containing nerve fibers, projecting from PVN to areas in the brainstem, exert a stimulatory effect on areas involved in the control of the function of brainstem areas involved in stress regulation, e.g., the LC, the rostroventrolateral medulla (RVLM), an important center for regulation of blood pressure, and the NTS. In this way, the function of the hypothalamic and the brainstem stress systems are interrelated.
Administration of Oxytocin Inhibits the Effect of the Sympathetic Nervous System and the HPA Axis
Oxytocin and Blood Pressure
Administration of oxytocin may increase or decrease blood pressure, depending on experimental conditions, by acting on different sites involved in the control of blood pressure. When oxytocin is administered into the brain, blood pressure decreases after a certain delay. After repeated administration of oxytocin, a long-term decrease of blood pressure is induced (Petersson et al., 1996b; Petersson, Hulting, Anderson, et al., 1999).
The oxytocin-mediated decrease of blood pressure is induced as a consequence of decreased activity in the sympathetic nerves, which regulate the function in the cardiovascular system. Oxytocinergic neurons originating in the paraventricular nucleus (PVN) project to many regions involved in cardiovascular control, such as the nucleus tractus solitarius (NTS), nucleus ambiguus, Locus Coeruleus (LC) the dorsal motor nucleus of the vagus nerve (DMX), the raphe nuclei, the rostroventrolateral medulla (RVLM), and the intermediolateral cell column in the thoracolumbar segments of the spinal cord and, therefore, these areas may have been involved in the decrease of blood pressure induced by oxytocin (Petersson et al., 1996b; Petersson, Lundeberg, et al., 1999b).
Oxytocin and the HPA Axis
Administration of oxytocin results in a decrease of cortisol levels (Petersson, Hulting, & Uvnäs-Moberg, 1999). Oxytocin may decrease cortisol secretion by several parallel mechanisms. Oxytocin released within the PVN decreases CRF secretion. Oxytocin released from nerves in the anterior pituitary decreases the secretion of ACTH. Oxytocin in the circulation decreases cortisol secretion directly from the adrenals. As will be described more in the chapters on skin-to-skin contact, oxytocin also influences cortisol secretion by actions in areas in the brainstem involved in the control of sympathetic nervous tone.
Long-Term Effect on Blood Pressure and HPA Axis
Repeated exposure to oxytocin is associated with sustained anti-stress effects, e.g., a decrease of blood pressure and cortisol levels. The long-term decrease of blood pressure caused by repeated exposure to oxytocin seems to be mediated by activation of a specific kind of receptors, alpha-2 adrenoceptors, which exert inhibitory actions on noradrenergic transmission in the brain. This effect of oxytocin has been demonstrated by neurophysiological, immunohistochemical, pharmacological, and physiological techniques (Petersson, Eklund, & Uvnäs-Moberg, 2005; Petersson, Lundeberg, et al., 1999a; Petersson, Uvnäs-Moberg, Erhardt, & Engberg, 1998).
The sustained decrease of cortisol levels may involve an increased function of alpha-2 receptors discussed above and also a change in the function of other mechanisms involved in the regulation of the HPA axis in the brain. For example, the function of the GR and MR receptors in the hippocampus is changed after repeated exposure of oxytocin (Petersson, Hulting, Andersson, et al., 1999; Petersson & Uvnäs-Moberg, 2003).
Decreased Activity in the Noradrenergic Neurons of the LC
Administration of oxytocin has been demonstrated to induce an anxiolytic effect (Uvnäs-Moberg et al., 1994). The anxiolytic effect is exerted in the amygdala and the reaction to stress is reduced. As a consequence of the reduced stress reactivity, the activity of the noradrenergic nerves in the LC is decreased, and thereby the activity in the sympathetic nervous system and the HPA axis, as the activity of both these systems are stimulated by noradrenaline.
Suckling Stimulates Oxytocin Release via Activation of Somatosensory Nerves
Oxytocin is released from magnocellular neurons in the SON and PVN into the circulation in response to suckling to induce the milk ejection reflex. It is also released from oxytocinergic nerves originating from parvocellular neurons in the PVN, which project to many different areas in the brain. Some oxytocinergic nerves project to the hypothalamus and areas in the brainstem involved in the control of the HPA axis and the sympathetic nervous system. These oxytocinergic nerves are of utmost importance for the oxytocin-mediated anti-stress effects caused by suckling.
Neurogenic Pathways Involved in Oxytocin Release by Suckling
During suckling, both somatosensory nerves, originating in the nipple and entering the central nervous system via the spinal cord, and sensory nerves, that bypass the spinal cord and project directly to the NTS—“the vagal nerve afferents”—are activated (Eriksson, Lindh, et al., 1996).
On their way to the hypothalamus, the neurogenic impulses induced by suckling relay in the NTS. In this area, afferent nervous pathways that connect with the SON and PVN of the hypothalamus are activated. As the magnocellular oxytocin-containing neurons are activated, oxytocin is released into the circulation, and as the parvocellular oxytocin-containing neurons are activated, oxytocin is released into the brain.
Suckling Induces Oxytocin Release from Parvocellular Neurons Projecting to the Hypothalamus and Brainstem
Some of the anti-stress effects induced by suckling, e.g., the lowering of blood pressure in nursing rats, are due to a release of oxytocin from parvocellular neurons emanating in the PVN, projecting to brainstem areas involved in the control of the activity of the sympathetic nervous system, such as nucleus tractus (NTS), nucleus ambiguus, Locus Coeruleus (LC), the dorsal motor nucleus of the vagus nerve (DMX), the rostroventrolateral medulla (RVLM), and the intermediolateral cell column in the thoracolumbar segments of the spinal cord (Buijs, 1983; Buijs et al., 1985; Sofroniew, 1983; Stern & Zhang, 2003; Zerihun & Harris, 1983; Zimmerman et al., 1984).
Oxytocin released from oxytocinergic fibers emanating from parvocellular neurons in the PVN in response to suckling may also be involved in the control of the HPA axis. Oxytocin-containing fibers reach areas in the hypothalamus and the anterior pituitary involved in the control of the HPA axis (Buijs et al., 1985; Sofroniew, 1983).
Decrease of Stress Levels and Stress Buffering
As the noradrenergic tone in the LC is lowered by suckling, the reactivity to certain types of stress responses will also be decreased. In this way, oxytocin released in response to suckling not only induces a direct anti-stress effect on the HPA axis and the sympathetic nervous system, it also dampens the effects of stress in the LC and may therefore also exert a stress-buffering effect.
When the LC, the NTS, and adjacent areas involved in the control of autonomic tone are repeatedly exposed to oxytocin during suckling, the function of the alpha-2 receptors gradually increases. As a consequence, the activity in the central noradrenergic system and the sympathetic nervous system is reduced in a long-term way and the function of other transmitter systems may also be increased (Diaz-Cabiale et al., 2000; Petersson, Eklund, et al., 2005; Petersson, Hulting, Andersson, et al., 1999; Petersson, Uvnäs-Moberg, et al., 1998).
- Suckling induces calm in lactating animals.
- Suckling may reduce physical activity in lactating animals.
- Suckling reduces reactivity to stressors that do not activate protection of the offspring.
- Suckling reduces basal energy expenditure.
- All these adaptations help the mother focus on her offspring and use energy for milk production.
- The effects are induced via suckling-induced oxytocin release in the brain.
- Oxytocinergic fibers projecting to brainstem areas involved in the control of stress reactions and sympathetic nervous tone, and oxytocinergic fibers within the hypothalamus, play a major role in these anti-stress reactions.
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Photo with title courtesy of Rosie Evans.