Chapter 11: Stress Flashcards
What is Stress?
Stress is a state of threatened homeostasis or disruption in homeostatic balance
The thing responsible for the imbalance is the stressor.
Can be environmental, physiological, psychosocial.
The body’s response to the imbalance is the stress-response.
Suite of physiological and behavioral responses that help to reestablish homeostasis.
Non-specific i.e. all stressors elicit a similar stress response
The body’s response to imbalance?
The body’s response to the imbalance is the stress-response.
Suite of physiological & behavioral responses that help to reestablish homeostasis.
Non-specific, i.e. all stressors elicit a similar stress response
The Stress Response:
General Systems
1) SYMPATHETIC NERVOUS SYSTEM
2) HYPOTHALAMIC-PITUITARY-ADRENAL AXIS
3) OTHER BRAIN-DERIVED HORMONES
Sympathetic Nervous System
Projections to virtually every organ in body where norepinephrine (NE) released
Adrenal medulla secretes epinephrine (aka adrenaline) and norepinephrine (NE)
“Fight or flight”: low priority systems shut down; blood & oxygen sent to the most necessary parts of the body.
HPA AXIS
Involved in Stress Response
The paraventricular Hypothalamus (PVN) releases corticotrophin-releasing hormone (CRH), which affects the anterior pituitary
The anterior Pituitary releases tropic hormone: ACTH
In response to ACTH, the Adrenal glands release cortisol or corticosterone (CORT)
CORT influences many neurons in the brain, increasing the release of several neurotransmitters
Amygdala also stimulates CRH release in the PVN
ACTH
Adrenocorticotropic hormone, also known as corticotropin
Tropic hormone.
Produced and Released by Anterior Pituitary
An important component of the hypothalamic-pituitary-adrenal (HPA) axis and is often produced in response to biological stress (along with its precursor corticotropin-releasing hormone from the hypothalamus).
A polypeptide hormone produced and secreted by the anterior pituitary gland.
Its principal effects are increased production & release of cortisol by the cortex of the adrenal gland.
ACTH is also related to the circadian rhythm in many organisms.
Cushing’s disease, Addison’s disease.
A polypeptide hormone produced and secreted by the anterior pituitary gland.
Primary adrenal insufficiency, called Addison’s disease, occurs when adrenal gland production of cortisol is chronically deficient, resulting in chronically elevated ACTH levels.
When a pituitary tumor is the cause of elevated ACTH (from the anterior pituitary) this is known as Cushing’s disease and the signs & symptoms of the excess cortisol (hypercortisolism) is known as Cushing’s syndrome.
Conversely, deficiency of ACTH is a cause of secondary adrenal insufficiency, often as a result of hypopituitarism.
In addition to its endogenous role, ACTH is used clinically as a diagnostic agent in assessing adrenal function.
CORT
Adrenal glands release cortisol or corticosterone (CORT) in response to ACTH
CORT influences many neurons in the brain, increasing the release of several neurotransmitters
Amygdala stimulates the release of _____ in the ____.
Amygdala stimulates the release of Corticotrophin-Releasing Hormone (CRH) in the Paraventricular Hypothalamus (PVN).
Other hormones involved in the stress response:
Posterior pituitary: vasopressin
Anterior pituitary: β-endorphin, prolactin
Pancreas: glucagon
Hormonal Changes in Humans in Response to Social Stressors
10% Increase in passengers caused high epinephrine recreation… high stress
Levels of epinephrine and norepinephrine speak at graduate exams, showing the stress response students have to exams.
Cortisol concentrations are altered by the stress of parachute jumps
pre-jump: baseline
Right before jump: super high
Right after jump: even higher
Cortisol before & after was decreased until 5 days after initial jump.
11 days, a little increased cortisol before & after.
The stress response:
Acute vs. Chronic
In the short term, the stress response produces adaptive changes that help the animal cope with emergency situations
Ideally, the stress response is initiated by stressful stimuli and then is deactivated shortly after.
If the stress response is activated too long, too frequently (i.e. chronic stress), or if is not activated for a physiological reason (i.e. psychological and social stressors), the stress response can be maladaptive and can endanger health.
Chronic Stress Has Systemic Effects:
Brain
Dendritic Atrophy
Enhanced Benzodiazepine Tone
Impaired Neurogenesis & Synaptic Plasticity.
Chronic Stress Has Systemic Effects:
Heart
Basal Hypertension
Sluggish Response to Stress
Sluggish Recovery from Stress
Pathogenic Cholesterol Profile
Chronic Stress Has Systemic Effects:
Ovary
Decreased Levels of Gonadal Hormones
Increased Risk of Anovulation and Miscarriage
Chronic Stress Has Systemic Effects:
Testis
Testicular Atrophy
Decreased Levels of Gonadal Axis Hormones
Chronic Stress Has Systemic Effects:
Adrenal Gland
Elevated Basal Levels of Glucocorticoids
Sluggish Response to Stress
Sluggish Recovery from Stress
Feedback Resistance
Chronic Stress Has Systemic Effects:
Immune System
Basal Immunosuppression
Decreased Immune Responsiveness to Challenges.
Metabolic Stress Response
2 metabolic responses to stress which increase glucose in the blood stream to provide energy:
1) Prevent energy storage via glucagon inhibition of insulin secretion from pancreas
2) Release of energy store via increased secretion of glucocorticoids, catecholamines (i.e. NE and E), glucagon
Lipolysis (triglycerides into fatty acids)
Glycogenolysis (glycogen into glucose)
Proteolysis (proteins into amino acids)
Gluconeogenesis (fatty acids and amino acids into glucose)
Pathological consequence:
Lack of energy reserves leads to myopathy (muscle loss), weakness and fatigue
Prevent energy storage via glucagon inhibition of insulin secretion from pancreas
Metabolic stress response.
The body prevents energy storage, promotes energy release by making the pancreas stop releasing insulin.
Glucagon inhibits insulin release.
Release of energy store via increased secretion of glucocorticoids, catecholamines (i.e. NE and E), glucagon
Metabolic stress response.
The body promotes energy release by secreting more Glucocorticoids, Catecholamines (i.e. NE and E), and Glucagon
Lipolysis (triglycerides into fatty acids)
Glycogenolysis (glycogen into glucose)
Proteolysis (proteins into amino acids)
Gluconeogenesis (fatty acids and amino acids into glucose)
Gluconeogenesis
Process by which fatty acids and amino acids are changed into glucose
Metabolic stress response.
Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as pyruvate, lactate, glycerol, and glucogenic amino acids.
Lipolysis
triglycerides are broken down into into fatty acids
Metabolic stress response.
the breakdown of lipids.
Involves hydrolysis of triglycerides into glycerol and free fatty acids.
The following hormones induce lipolysis:
epinephrine, norepinephrine, ghrelin, growth hormone, testosterone, and cortisol.
Proteolysis
The breakdown of proteins into smaller polypeptides or amino acids.
Metabolic stress response.
Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years.
Proteolysis is typically catalysed by cellular enzymes called proteases, but may also occur by intra-molecular digestion.
The following hormones induce lipolysis:
epinephrine, norepinephrine, ghrelin, growth hormone, testosterone, and cortisol.
Metabolic stress response.
Glycogenolysis
glycogen breaks down into glucose
Metabolic stress response.
Glycogenolysis is the breakdown of glycogen (n) to glucose-6-phosphate and glycogen (n-1).
Glycogen branches are catabolized by the sequential removal of glucose monomers via phosphorolysis, by the enzyme glycogen phosphorylase.
Pathological Consequences of Metabolic Stress Response.
Lack of energy reserves leads to myopathy (muscle loss), weakness, and fatigue
Cardiovascular Stress Response
Increase Cardiovascular Tone:
Stimulation of SNS: Increased heart rate, blood pressure, decreased blood flow to some organs (i.e. digestive tract)
Increased Secretion of Vasopressin: Increased blood volume and blood pressure
Pathological Consequence:
Chronic hypertension damages heart muscle, weakens blood vessel walls, promotes deposition of cholesterol, and the formation of plaques.
Over time, could lead to heart attack and stroke.
Increase Cardiovascular Tone:
Stimulation of SNS:
Increased heart rate, blood pressure, decreased blood flow to some organs (i.e. digestive tract)
Increased Secretion of Vasopressin:
Increased blood volume and blood pressure
Cardiovascular Stress Response
Gastrointestinal Stress Response
Inhibition of GI tract:
primarily mediated by shift from parasympathetic to sympathetic tone
Pathological consequence:
Gastric ulcers: stress makes the stomach more vulnerable to certain damaging bacteria which increase inflammation and compromise the ability of cells lining the walls of the stomach to defend themselves against acid
GI tract:
Stress and the Microbiome
We are colonized by billions of bacteria, many are protective
Stress changes makeup of this microbiome
Bacteria can signal to the brain: Make serotonin, hormones like testosterone
Changes in gut microbes could possibly lead to increased stress-related behavior (anxiety, depression)
Reproductive Stress Response
Inhibition of Reproduction:
- Hypothalamus: CRH and β-endorphin inhibit GnRH
- Pituitary: GC & Prolactin cause reduced responsiveness to GnRH, which causes decreased LH & FSH release
- Gonads: GC decreases sensitivity to LH
In females: secretion of E & P and the release of an egg less likely and reduces chances that a fertilized egg will implant into the uterine wall
In males: decreased T secretion and sperm production
Pathological consequence:
Anovulation, infertility, impotency, loss of libido
Luteinizing Hormone (LH) is important for ________.
LH is important for the production of hormones
The Hypothalamus’ CRH and β-endorphin inhibit ______
The Hypothalamus’ CRH and β-endorphin inhibit GnRH
GnRH
Gonadotropin-releasing hormone (GnRH)
Also known as follicle-stimulating hormone–releasing hormone (FSH-RH), luteinizing hormone–releasing hormone (LHRH), gonadoliberin, luliberin in its endogenous form, gonadorelin (INN) in its pharmaceutical form
A releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the Anterior Pituitary.
GnRH is a tropic peptide hormone synthesized and released from GnRH neurons within the hypothalamus.
The peptide belongs to gonadotropin-releasing hormone family.
It constitutes the initial step in the hypothalamic–pituitary–gonadal axis.
Increased Cardiovascular and Cardiopulmonary Tone are damaging.
Prolonged stress has been linked to the development of high blood pressure (hypertension), and other cardiovascular problems.
Stress elevates the levels of several hormones, but suppresses other hormones such as ______ and ______.
Stress elevates the levels of several hormones, but suppresses other hormones such as testosterone and progesterone.
This can eventually lead to suppression of ovulation, impotency, and loss of libido.
Stress elevates the levels of several hormones, but suppresses other hormones such as testosterone and progesterone.
This can eventually lead to suppression of ____, ____, and _____.
Stress elevates the levels of several hormones, but suppresses other hormones such as testosterone and progesterone. This can eventually lead to suppression of ovulation, impotency, and loss of libido.
Acute stress mobilizes internal energy stores, which is highly adaptive.
However, prolonged stress can lead to fatigue and muscle wasting.
The temporary suppression of immune responses makes sense because the stress response demands a rapid mobilization of energy.
Immune responses extend longer than the immediacy of a demanding situation would require.
Long-term stress is believed to cause oxidative damage in the brain, which may contribute to neural degeneration.
Prolonged stress can cause the altered cognition and sensory thresholds, as well as accelerated neural degeneration during aging.
Psychogenic dwarfism can be caused by extremely stressful situations, such as being locked in a closet, living in a war zone, etc.
Bone decalcification and dwarfism can be consequences of extreme childhood stress.
Children in such traumatizing situations may lag years behind the normal growth rate.
Chronic stress may lead to the formation of ____ in the digestive system.
Chronic stress may lead to the formation of gastric ulcers.
THE LOGIC OF THE STRESS RESPONSE
- There is a need for immediate energy/ energy storage is prevented
- > increase glucose in blood stream.
glucocorticoids prevent glucose uptake by cells
glucagon mobilizes stored glycogen
Insulin is inhibited (no glucose storage)
-> oxygen must be delivered to muscles and other cells
Breathing rate increases (sympathetic NS)
Heart-rate increases (sympathetic NS)
Blood pressure increases (sympathetic NS + vasopressin)
Water is retained to increase blood volume (vasopressin)
- Anabolic Processes are inhibited (why waste energy on processes important tomorrow?)
- > digestion is curtailed
- > reproductive processes are inhibited
- > immune system inhibited
- > suppression of inflammation
- > no pain perception “stress induced analgesia”
Consequences of a prolonged stress response on growth:
Inhibition of Growth: Increased somatostatin (GH-inhibiting hormone) release from hypothalamus
Pathological consequence: Young–> psychosocial dwarfism (Kaspar Hauser syndrome)
Adults–> growth & repair processes
somatostatin
a hormone secreted in the pancreas and pituitary gland that inhibits gastric secretion and somatotropin release.
A polypeptide hormone that is mainly produced in the hypothalamus.
Inhibits the secretion of various other hormones, including somatotropin, glucagon, insulin, TSH, and gastrin.
Differences between all the “G” hormones
Gonadotropin-releasing hormone (GnRH):
A decapeptide hormone from the hypothalamus that regulates FSH & LH release from the Anterior Pituitary. Stress chapter.
Growth hormone (GH)
A protein hormone that stimulates somatic (body) growth.
GH, however, does not directly induce skeletal growth; it stimulates the production of growth-regulating substances (somatomedins) by the liver, kidneys, etc.
Somatomedins cause bone to take up sulfates, leading to growth.
GH and somatomedins also stimulate protein synthesis.
Growth hormone-inhibiting hormone (GHIH):
A peptide hormone secreted from the hypothalamus thatreduces the secretion of growth hormone by the anterior pituitary gland.
Growth hormone-releasing hormone (GHRH):
A polypeptide hormone that is released from the arcuate nucleus of hypothalamus that provokes the secretion of growth hormone from the anterior pituitary gland.
Stress Response & Analgesia
Stress-induced analgesia (pain reduction): B-endorphin
Pathological consequence: ???
- Maybe blunted pleasure responses if long-term exposure leads to receptor desensitization.
- Maybe risk for drug abuse
Pancreas
A composite gland with both endocrine & exocrine functions.
In humans, the pancreas is located within the curve of the duodenum behind the stomach and liver, and secretes digestive enzymes (exocrine function), insulin, glucagon, and somatostatin (endocrine function), as well as bicarbonate.
Immune Function
Acutely, Glucocorticoids enhance some aspects of immune function (e.g. trafficking of immune cells to skin where injury might occur) but inhibit other aspects of immune function (e.g. inflammatory response)
Pathological consequence:
Sustained inhibition of inflammatory response may make it more difficult for body to heal itself after injury.
Sustained suppression of the immune system increases vulnerability to infections because GCs suppress lymphocytes
Glucocorticoids (GCs)
Glucocorticoids (GCs) are a class of steroid hormones which bind to the glucocorticoid receptor (GR), that is present in almost every vertebrate animal cell.
The name glucocorticoid (glucose + cortex + steroid) derives from its role in the regulation of the metabolism of glucose, its synthesis in the adrenal cortex, and its steroidal structure. Another synonym is glucocorticosteroid.
GCs are part of the feedback mechanism in the immune system which reduce certain aspects of immune function, such as reduction of inflammation.
They are used in medicine to treat diseases caused by an overactive immune system, such as allergies, asthma, autoimmune diseases, and sepsis.
GCs have many diverse (pleiotropic) effects, including potentially harmful side effects, and as a result are rarely sold over the counter. They also interfere with some of the abnormal mechanisms in cancer cells, so they are used in high doses to treat cancer.
GCs cause their effects by binding to the glucocorticoid receptor (GR). The activated GR complex, in turn, up-regulates the expression of anti-inflammatory proteins in the nucleus (a process known as transactivation) and represses the expression of proinflammatory proteins in the cytosol by preventing the translocation of other transcription factors from the cytosol into the nucleus (transrepression).
Glucocorticoids are distinguished from mineralocorticoids and sex steroids by their specific receptors, target cells, and effects.
Glucocorticoids are chiefly produced in the zona fasciculata of the adrenal cortex.
Cortisol (or hydrocortisone) is the most important human glucocorticoid. It is essential for life, and it regulates or supports a variety of important cardiovascular, metabolic, immunologic, and homeostatic functions.
Various synthetic glucocorticoids are available; these are used either as replacement therapy in glucocorticoid deficiency or to suppress the immune system.
The Hippocampus and Termination of Stress Response
Hippocampus (and prefrontal cortex too)….
has dense concentration of glucocorticoid receptors (GRs)
participates in negative feedback regulation of the HPA axis
When Hippocampus binds cortisol, it leads to inhibition of CRH release from PVN
Prefrontal cortex does this too
PVN and pituitary also directly sensitive to GCs
When Hippocampus binds cortisol, it leads to inhibition of ______ release from ______
When Hippocampus binds cortisol, it leads to inhibition of CRH release from PVN
The Stressed Hippocampus:
Acute vs. Chronic
Acute stress:
Improves memory
Enhances long term potentiation (LTP)
Chronic stress: Impairs LTP. Shrinks dendrites. Causes loss of dendritic spines Reduces adult neurogenesis Impairs memory Increases anxiety & depression (both regulated by hippocampus) These effects of chronic stress are due to glucocorticoids
The Stressed Amygdala
Chronic stress:
Increased dendrites and dendritic spines.
Amygdala becomes hyperactive (leads to anxiety, fear, etc).
Increased anxiety & depression.
These effects of chronic stress are due to glucocorticoids.
Connection between amygdala, hippocampus, and prefrontal cortex important for fear, anxiety, and PTSD
Factors that affect stress responsiveness
Pre-natal Environment Post-natal Environment Social Support Prior Experience Age Sex Psychological variables
Prenatal Environment and Stress
Offspring of mothers stressed during pregnancy…
- Had impaired negative feedback of the HPA axis, which increases basal CORT levels.
- Due to deceased hippocampal glucocorticoid receptors in the offspring.
- Adrenalectomy of the mother prevents the elevated stress response in offspring
Prenatally stressed human infants:
Reduced birth weight Developmental delays Attentional deficits Hyper-anxiety Impaired social behaviors Impaired stress coping strategies as adults May increase incidence of schizophrenia
In the Netherlands, there was increased incidence of schizophrenia in individuals who were in utero during German invasion
Postnatal Environment
Short-term, mild stressors improve response to stress as adults, i.e. stress immunization
But…
Long-term moderate to severe stressors impair response to stress as adults
Early stressful experiences affect reactions to stress:
Stress-IMMUNIZED Offspring
More Maternal Care
More adaptive pups
Decreased HPA response to stress
Increased Hippocampal GR
Early stressful experiences affect reactions to stress
later in life
Stress-SUSCEPTIBLE Offspring
Prolonged Maternal Separation
- —> Decreased LG-ABN
- —> Increased HPA response to stress + Decreased Hippocampal GR
LG-ABN
licking/grooming and arched-back nursing
Early stressful experiences affect reactions to stress later in life:
Children & Orphanages
Children who were adopted from the orphanages before 8 months of age were able to develop stress coping ability almost as well as regular children.
Once the child was older that * months, it was harder to rescue the affects of having lived in the orphanage. Their baseline cortisol levels were higher.
Postnatal Environment (humans)
Ace Study:
Adverse early childhood experiences linked to stress related disorders, drug/alcohol abuse, cancer, cardiovascular disease, early death
True of low SES families too
Many more stressors
The ACE Score test
Epigenetics
Heritable changes in phenotype or gene expression caused by mechanisms other than changes in the underlying DNA sequence
These changes may last for multiple generations despite the fact that there is no change in the underlying DNA sequence of the organism
Non-genetic-factors cause the organism’s genes to behave (i.e. “express themselves”) differently
Epigenetic Mechanisms
1) Methylation state:
- methylation silences genes
- demethylation of a gene leads to protein expression
2) Chromatin structure:
DNA in eukaryotic cells is wrapped around proteins called histones (DNA + histones = chromatin)
Compactness of the histones in a particular region of chromatin determines how readily transcription factors access promoters in the DNA
Variety of processes can alter chromatin structure including acetylation which decreases the binding of histones to DNA thereby increasing access of transcription factors to promoters
Methylation
methylation silences genes
de-methylation of a gene leads to protein expression
Epigenetic Mechanism
Chromatin structure:
DNA in eukaryotic cells is wrapped around proteins called histones
DNA + histones = chromatin
Compactness of the histones in a particular region of chromatin determines how readily transcription factors access promoters in the DNA
Variety of processes can alter chromatin structure, including acetylation which decreases the binding of histones to DNA thereby increasing access of transcription factors to promoters
chromatin
DNA + histones = chromatin
acetylation
Alters chromatin structure by decreasing the binding of histones to DNA, thereby increasing access of transcription factors to promoters
Acetylation of the lysine residues at the N terminus of histone proteins removes positive charges, thereby reducing the affinity between histones and DNA.
This makes RNA polymerase and transcription factors easier to access the promoter region.
Therefore, in most cases, histone acetylation enhances transcription while histone deacetylation represses transcription.
Epigenetic influences of maternal behavior on stress offspring
Stress leads to decreased glucocorticoid receptor expression in hippocampus
less negative feedback on HPA axis
more stress responsive
Epigenetic influences of maternal behavior on stress offspring
Early life stress leads to decreased methylation of vasopressin promoter in hypothalamus, which leads to:
- Increased vasopressin in response to stress
- Bigger HPA axis response to stress throughout life
Early life stress leads to _____ of vasopressin promoter in _____.
Early life stress leads to decreased methylation of vasopressin promoter in the hypothalamus.
Epigenetics in humans
Brains of suicide victims revealed same epigenetic change in expression of the GR but only in those victims that had a history of being abused or neglected as children
Implication: early abuse modified expression of genes, making people less able to handle stress and thus more likely to become depressed and commit suicide
Social Factors:
Vervet monkeys
Most studies show that dominant animals have lower CORT than subordinate animals, particularly with social unrest.
Example: Vervet monkeys in captivity
Form social hierarchy where dominants constantly harass subordinates
Subordinate animals died at younger age and exhibited signs of chronic stress including enlarged adrenal glands, ulcers, and neural degeneration in the hippocampus
The relationship between dominance and Glucocorticoids doesn’t hold true for all species….
In African hunting dogs, subordinates have the lowest CORT and the dominants have the highest CORT
Sustained suppression of the immune system increases vulnerability to infections because…..
Glucocorticoids suppress lymphocytes.
Social support serves as a “stress buffer”
Social support has many beneficial effects on various aspects health and well being:
Mice who live alone before heart attack or stroke experience more neurological damage and more harmful inflammation as compared to mice housed with partners.
In humans, social support has been shown to accelerate and improve recovery from a variety of illnesses including cancer, stroke, heart disease.
Previous Experiences Can Modify Stress Responses
Repeated experience can desensitize response to stress
Repeated experience can also sensitize response to stress
….
Whether sensitization or desensitization occurs depends mostly on 2 factors…
Type of stressor:
Mild stressors desensitize.
Strong stressers sensitize.
Same stressor repeated leads to desensitization while changing stressor (i.e. chronic mild unpredictable stress) sensitizes.
Age and Stress
HPA axis tends to become less sensitive to negative feedback regulation as individuals age, resulting in higher glucocorticoid levels after stress.
More age –> greater susceptibility to stress
Sex Differences in Stress
Rodents:
Females higher basal and stress-induced CORT.
Activational—> ovariectomy removes these sex diffs, E2 treatment restores.
Higher glucose utilization in females than in males following stress, esp. in hippocampus, hypothalamus, amygdala
Humans:
Females higher basal and stress-induced CORT.
Females have higher ACE scores on average.
Females higher likelihood of stress-related disorders.
Psychological variables that affect stress responsiveness
Control
Predictability
Outlet for Frustration
Controllability
“Yoked Control” design is a popular way to assess the effects of controllable vs. uncontrollable stressors
Animal 1 receives a shock but can turn it off by turning the barrel
Animal 2 receives same duration shock as Animal 1 but can not turn the shock off
Results:
Animal 2 has higher CORT and more ulcers than Animal 1 even though the animals were exposed to exactly the same duration of shocks.
The only difference was that Animal 1 could control the stressor whereas Animal 2 could not.
Predictability
“Yoked Control” design is also used to assess the effects of predictable versus unpredictable stressors
Flashing light notifies animal 1 that shock is coming.
Animal 2 receives same duration shock. But there is no light, so the animal never knows when to expect shock.
Results:
Animal 2 has higher CORT and more ulcers than Animal 1 even though the animals were exposed to exactly the same duration of shocks.
Only difference was that Animal 1 could predict onset of shock and Animal 2 couldn’t.
Outlets for Frustration
The ability to engage in displacement behavior (i.e. having an “outlet”) can ameliorate the effects of stress
Example: chewing on wooden stick or attacking another rat
In humans: hobbies, exercise, meditation
