The Neural Substrate of Stress

Recall

Role of hypothalamus in the fight or flight response ; sham rage

Different components of a stress response

Behavioural

Autonomic

Endocrine

Sensory

Notes

PNS and stress

• What is stress ?

  • A feeling triggered by threat

  • Acute stress responses are good and adaptive. They prepare the organism for an active response to deal with threat

  • Chronic stress responses are not good and not adaptive. They weaken our body and affect our health

  • Stress responses originate from the brain and are put together inside the brain

  • How does it work?

• Transection Studies (Cannon and Bard)

  • The hypothalamus is crucial for the expression of stress responses and it is under the inhibitory control of higher structures (cortex)

  1. Decerebration (removal of cortex and thalamus) causes sham rage: an exaggerated, undirected but integrated emotional stress reaction (fight / flight)

  2. Transection below hypothalamus: no sham rage, incomplete stress response and only with strong stimuli

• Electrical stimulation studies (Hess)

  • Emotional responses are integrated at the level of the hypothalamus and midbrain

  1. Stimulation of the hypothalamus produces integrated flight/fight response (defence reaction)

  2. Stimulation of the midbrain periaqueductal gray (PAG) also

  3. Stimulation in brainstem below PAG never produces an integrated fight/flight response

     1. If you only started at the brainstem for example, you would only get bits and pieces of response, rather than the full defence reaction

• Components of a stress response

  1. Behavioural component

     1. Arrest with increased muscle tone, then fight or flight.

  2. Autonomic component

     1. Increase in heart rate, blood pressure, skin vasoconstriction (goes white), redistribution of blood flow from gut to muscles, sweating, interrupted gut function

  3. Endocrine component

     1. Release of cortisol

  4. Modulation of sensory input → pain inhibition (hypoalgesia)

• Autonomic components of stress responses

  • Autonomic function is mediated by the Autonomic Nervous System (ANS) the part of the nervous system that controls the viscera

• What is the ANS?

  • It controls smooth muscles, and glands (viscera), and the cardiac muscle

  • Autonomic = autonomous = not under voluntary control

  • The ANS contributes to the regulation of the “internal milieu” = homeostasis

  • The ANS has two branches:

    • Sympathetic if nerve passes through the paravertebral sympathetic chains

    • Parasympathetic if not

• Anatomy of the ANS

  • Unlike somatic system, the autonomic system output relays in autonomic ganglia which magnifies the signal

  • Preganglionic neurons are in the CNS and have myelinated axons

  • Postganglionic neurons are in the ganglia and have unmyelinated axons

• Sympathetic preganglionic neurons are located in the thoracic cord T1-L2

  • Sympathetic postganglionic neurons are located in the:

    1. Paravertebral ganglia of left and right sympathetic chains

    2. Prevertebral ganglia

    3. Adrenal medulla → can be alike a ganglia itself

  • Parasympathetic preganglionic neurons are located:

    • in brainstem and send their axons via cranial nerves III, VII, IX and X (vagus nerve)

    • in sacral cord (S1 - S4)

  • Parasympathetic postganglionic neurons are small, scattered and located close to the target organ

<aside> 💡 Sympathetic preganglionic axons are short whilst postganglionic axons are long

Parasympathetic preganglionic axons are long while postganglionic axons are short.

</aside>

• Sympathetic preganglionic fibres enter the sympathetic chain via white communicating ramus (myelinated)

• Sympathetic postganglionic fibres leave the sympathetic chain via gray communicating ramus (unmyelinated)

• Parasympathetic anatomy summary

• Neurotransmitters in the ANS

  • Both sympathetic and parasympathetic preganglionic neurons use acetylcholine as their neurotransmitter

  • All sympathetic postganglionic neurons use norepinephrine as their neurotransmitter (except those to sweat glands : ACh)

  • Parasympathetic postganglionic neurons use acetylcholine as their neurotransmitter

• Receptors in the ANS

  • Sympathetic and parasympathetic preganglionic neurons act via the same nicotinic receptors

  • Sympathetic postganglionic neurons act via alpha and beta adrenergic receptors

  • Parasympathetic postganglionic neurons act via muscarinic receptors

  

• Physiology of the ANS

  • Sympathetic and parasympathetic branches tend to have opposite functions:

    • On the pupils

    • On the heart

    • On the guts

    • On salivation

    • On the bladder

  • But can also have complementary functions

    • on genitals (erection / ejaculation)

  • Some functions are only controlled by sympathetic system

    • Vasoconstriction

    • Sweating

• OVERALL - Physiology of ANS

  • The sympathetic systems are active during wakefulness and spends energy

  • The parasympathetic system is active during rest and works to restore energy

  • The dynamic regulation of the sympathetic and parasympathetic systems contribute to homeostasis

• Autonomic function is regulated by lower brainstem centres (pons and ventral medulla) whose normal function is to maintain homeostasis

<aside> 📌 SUMMARY:

</aside>

Date: June 23, 2024

Topic: Physiology of the ANS

Recall

Notes

• Autonomic function is regulated by lower brainstem centres (pons and ventral medulla) whose normal function is to maintain homeostasis

  • They receive so much sensory input

Autonomic components of a stress response

• Hypothalamic neurons project to brainstem centres and during a stress response override their homeostatic activity to prepare the organism for a fight/flight response

1. The autonomic adjustments of a stress response are mediated by the sympathetic division of the autonomic nervous system

2. Noradrenaline (NA) is released from sympathetic nerves into organs (e.g. heart, blood vessels and gut)

3. Adrenaline (A) is released from the adrenal medulla into the blood stream to further magnify the sympathetic response.

• Effects of a sympathetic activation during a stress response:

  • Dilation of bronchioles → increases gas exchange in the lungs

  • Increased heart rate and heart contractility → increases blood circulation and perfusion of tissues

  • Constriction of blood vessels in the gut → diverts blood away from guts and increases blood pressure

  • Dilation of blood vessels in skeletal muscles → increases perfusion of muscles for intense muscle activity

  • Constriction of skin blood vessels in extremities → protects from blood loss? but cold hands, feet and pale face

  • Increase in metabolism → more energy and increased body temp

  • Activation of sweat glands → Limit the increase in body temp

  • Relaxation of bladder → urinate later

  • Impotence (no erection) → sex and stress don’t mix

Endocrine component

• Release of cortisol

  • Stress hormone

• This endocrine component is controlled by the pituitary gland or hypothalamus

• The pituitary gland controls many hormones and is divided into:

  • Anterior part - real gland

  • Posterior part - extension of hypothalamus

• Posterior pituitary

  • Is an extension of the hypothalamus

  • Oxytocin → Milk ejection, uterus contraction

  • Vasopressin → antidiuretic hormone (blood volume regulation)

  1. The paraventricular and supraoptic nuclei both contain neurons that produce vasopressin and oxytocin. The hormone, either vasopressin and oxytocin depending on the neuron, is synthesised in the neuronal cell body in the hypothalamus.

  2. The hormone travels down the axon to be stores in the neuronal terminals with the posterior pituitary

  3. On excitation of the neuron, the stores hormone is released from these terminals into the systemic blood for distribution throughout the body

  

• Anterior pituitary

  • Is a gland → not part of brain!

  1. Hypophysiotropic hormones (releasing hormones and inhibiting hormones) produced by neurons in the hypothalamus enter the hypothalamic capillaries

  2. These hypothalamic capillaries rejoin to form the hypothalamic-hypophyseal portal system. This vascular link passes to the anterior pituitary

  3. Here it branches into the anterior pituitary capillaries

  4. The hypophysiotropic hormones leave the blood across the anterior pituitary capillaries and control the release of anterior pituitary hormones

  5. On stimulation by the appropriate hypothalamic releasing hormone, a given anterior pituitary hormone is secreted into these capillaries

  6. The anterior pituitary capillaries rejoin to form a vein, through which the anterior pituitary hormones leave for ultimate distribution throughout the body by the systemic circulation

• Adrenocorticotropic hormone (ACTH) → Adrenal cortex

  • CRH-ACTH

    • CRH = corticotropin releasing hormone is the hypophysiotropic hormone for the release of ACTH

    • ACTH = adrenocorticotropic hormone = corticotropin

  

  • Endocrine components of a stress response

    • Hypothalamus releases CRH into the portal veins of the anterior pituitary gland

    • Anterior lobe of pituitary gland releases ACTH into the blood stream

    • ACTH acts on the cortex of the adrenal gland to release cortisol

    • Cortisol is a glucocorticoid; it acts everywhere. Main actions:

      • Gluconeogenesis

      • Increased metabolism

      • Decreased immune function

  

Modulation of sensory input

• Pain modulation during a stress response

  • Stress activates an endogenous pain modulating system

    • Wounded soldiers are less sensitive to pain (hypoalgesia)

    • Reduced sensitivity to pain during fight/flight

    • Involves endogenous opioids

    • Reynolds (1969) stimulated PAG and did surgery in non anesthetised rats

    • It is mediated by PAG and lower brainstem which in turn projects to the spinal cord to inhibit incoming pain signals

    • Clinical relevance. PAG stimulation is used in human to treat intractable pain

• What controls the hypothalamus and triggers stress

  • Physical stimuli: Pain

  1. Hypothalamic inputs from sensory relays in spinal cord and brainstem

  • Physiological stimuli: Cold, hunger, thirst, asphyxia

    1. Hypothalamic inputs from sensory relays in spinal cord and brainstem

    2. Hypothalamic sensors

  • Emotional stimuli: unpleasant memories, worries

    1. Hypothalamic inputs from limbic system and amygdala

• Emotional stress: Limbic system

  • A series of connected cortical structures located on the medial surface of the hemispheres

  • Part of it is ancient cortex

  • McLean proposed that the limbic system controls emotional behaviour and stress response

  • It processes sensory stimuli and gives them an emotional valence good or bad, depending on stores memories and acquired rules

  • It is the interface between the rest of the cortex and the hypothalamus

• Limbic System: Amygdala

  • Located in temporal lobe

  • Inputs from the limbic system and sensory relays

  • Output to hypothalamus

  • Triggers emotional responses to innate or learned dangers

  • Is able to learn and remember past events linked to an unpleasant or pleasant experience

  • Stimulation: Arousal, fear, rage

  • Bilateral lesion: placidity, unable to recognise facial expression of fear or anger

  • Amygdala: An fMRI experiment

    • fMRI shows increases in local blood flow in the LEFT amygdala

    • 3 conditions:

      • Threat: you may receive a shock

      • Safe: you will not receive a shock

      • Rest: please rest and wait

• Conscious modulation of stress: Prefrontal Cortex

  • The prefrontal cortex is most developed in humans → judgement, forecast, planning

  • The orbitofrontal part of the prefrontal cortex is linked to limbic system and amygdala

  • It is responsible for the conscious modulation of emotional responses

    • Abort them (I’m OK)

    • trigger them (I’m worried)

  • Lesion in a healthy person: careless, irresponsible, unable to see the consequence of actions “I don’t care”

  • Lesion in a psychopath: careless, yes, but less aggressive, less dangerous → prefrontal lobectomy

  • An fMRI study:

    • Young adult males were watched to watch erotic movies in 2 conditions:

      1. Watch movie without inhibition (like you are at home)

      2. Watch the movie but suppress sexual feelings

    • Found that in first condition → there is activation of right amygdala and hypothalamus

    • In condition 2 → amygdala activation is suppressed by prefrontal activation

<aside> 📌 SUMMARY:

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Date: June 26, 2024

Topic: Management of Stress

Recall

Notes

• Major responses to stress

• Recap components of an acute stress response

  • Behavioural component

    • Fight or flight

  • Autonomic component

    • The sympathetic pathway - “energy expenditure” prepares the body for fight or flight and other stress-related behaviours (increases heart rate, breathing rate, blood pressure, sweating)

    • The parasympathetic pathway - “energy conservation”…stress may cause an individual to lose bowel or bladder control

  • Endocrine component

    • Cortisol release

• Acute vs Chronic stress

• Prolonged stress

  • It can induce a chronic state of hyper-sympathetic activity and/or suppressed parasympathetic response

  • Stress is a trigger causing numerous disease processes to occur:

    • PTSD, IBD, IBS, peptic ulcer, GERD, chronic fatigue syndrome etc

  • Prolonged stress may also lead to life-threatening illnesses, e.g., hypertension, stroke, heart attack and cancer

• Emotional stress

  • The PFC, amygdala and hippocampus are interconnected to effect the stress response

  • Amygdala

    • Receives sensory information from the hypothalamus and cortex.

    • Responsible for the fear response, stimulating the release of CRH

  • Hippocampus

    • Receives information from the cortex and can inhibit the release of CRH to stop the stress response

  • Prefrontal Cortex (Regulates Cognition)

    • dmPFC reality checks and error monitoring

    • DIPFC regulates attention, thought and action

    • rIPFC inhibits inappropriate motor responses

    • vmPFC connects with subcortical structures that generate emotional responses, such as fear responses. Regulates emotion

• Normally (no stress)

  • Orbitofrontal PFC orchestrates regulation of behaviour, thought, emotion

    • Top-down regulation

    • PFC is most sensitive to detrimental effects of stress exposure

• During chronic stress:

  • Bottom-up again

  • Impaired PFC regulation and strengthened amygdala function

    • “Hyperdrive” of the amygdala

  • Response patterns switch from slow, thoughtful PFC regulation to the reflexive and rapid emotional responses of the amygdala and related subcortical structures

• vmPFC determines how well you handle stress

  • Neuroplasticity of the vmPFC is key to resilience-coping during stress - signals increased emotional and behavioural control

  • Hyperactivity of the vmPFC suggests you are likely to have maladaptive coping behaviours to stress

Sheds some light on the mechanisms involved in acute stress reactivity, adaptation and active coping…but underlying neural processes remain unclear

Non-pharmacological management of stress

• Physical

  • Breathing control

  • Relaxation (yoga, mindfulness meditation, sleep)

  • Cardiovascular fitness

• Perceptual/Relational

  • Letting go, improve communication, problem solving

• Psychotherapy

  • Rewiring the brain, vmPFC

  • Preferred first step; use medications adjunct therapy

    • Cognitive Behavioural Therapy (CBT)

      • Identified maladaptive thinking (assumptions and perceptions) → reconstruct more helpful and adaptive interpretation of the event → Better coping alleviates anxiety

    • Stress inoculation training (SIT)

      • Strengthen coping skills (relaxation methods, self-reward, grounding, problem solving) → anxiety reduction

    • Exposure based therapy

      • Confrontation with fear-eliciting stimuli in order to extinguish the conditioned response → Improves symptoms of exaggerated fear conditioning

    • Eye-movement desensitisation and reprocessing therapy (EMDR)

      • Hold traumatic image in mind while engaging in saccadic eye movements → interferes with working memory, lowers emotional arousal

      • Integrative approach (controversial), similar in efficacy to CBT

• Summary

  • Active/adaptive coping strategies

    • Use of reappraisal and reframing

      • Linked with resilience and positive health outcomes

  • Suppression, avoidance and rumination

    • Linked with negative health outcomes

Pharmacological management of stress

• Several neurotransmitters are implicated in stress, anxiety and depression: GABA, Glutamate, serotonin and noreadrenaline

• E.g. Anxiolytic drugs are used to modulate GABA neurotransmission

• Non-prescription alternatives:

  • 5-HTP (5-hydroxy-L-tryptophan)

    • 5-HTP is a derivative of the amino acid L-tryptophan, which is found in high-protein foods such as dairy products, fish, lean meats and the seed of Griffonia simplicifolia tree

• 5-HTP continued

  • 5-HTP is the precursor of serotonin (5-HT). It may be helped to promote neurotransmitter balance following daily use for 2-6 weeks

  • 5-HTP acts as a precursor to synthesise serotonin

  • 5-HTP is effective in depressed mood and mild to moderate mood swings caused by stress; tension and anxiety

• 5-HTP: improves conditions associated with low-serotonin

  • Depression, Obesity, Bulimia, Insomnia, Sleep apnea, PTSD, migraines, tension headaches, PMS

• Prescription Medications:

  • Anxiolytics

  • Anti-depressant drugs

    • SSRIs

    • Tricyclic antidepressants

  • Beta blockers

• Benzodiazepines

  • Many possible compounds

    • e.g. diazepam, nitrazepam, lormetazepam

  • Mechanisms of action

    • Bind to regulatory site on GABA-A receptor, distinct from GABA binding site

    • Increases frequency of opening of GABA activated Cl- channels → hyperpolarises post-synaptic neuron

    • Increase the affinity of GABA for the receptor

  Thus potentiate inhibitory effects of GABA throughout CNS.

• Orange areas below represent binding of benzodiazepines

  • Global reduction of binding sites for benzodiazepines in subject with panic disorder

    • Implies less GABA binding sites

Positron Emission Tomography scans demonstrate diminished binding of radioactive benzodiazepine in the frontal cortex of a patient with panic disorder

• Long term benzodiazepine treatment affects sleep quality

  • You wouldn’t use the drug for more than a few weeks → it can cause addiction and reduce sleep quality

  • During treatment phase, they get more sleep, but after there is a bad rebound where sleep is very bad after someone is coming off the drug

• Summary of Benzodiazepines

  • Highly effective against anxiety disorders, panic disorder

  • Anxiolytic actions are immediate (sedation and induction of sleep)

  • Usually start with low doses, then gradually increase the dosage until anxiety is controlled

  • Used for a short period (2-4 weeks). Fragments sleep, long-term may lead to dependence and withdrawal reactions

• Antidepressants

  • Tricyclics → inhibit reuptake of noradrenaline and serotonin from the synaptic cleft

    • Have a lot of side-effects: dry mouth, blurry vision

  • SSRIs (E.g. Fluoxetine)

    • First choice for a clinician

  • Monoamine Oxidase Inhibitors→ degrades noradrenaline and breaks down 5-HT, by inhibiting this enzyme allows the NTs to stay longer and activate the post-synaptic receptors

  

  • Monoamine Oxidase Inhibitors

    • Rarely used as a first line treatment due to interactions - cheese reactions

    • Indicated for patients who have failed to respond to more commonly used drugs for depression and anxiety

    • May be used in the treatment of panic disorder, PTSD, social phobia

    • E.g. Selegiline

    • Side effects: Orthostatic hypotension with dizziness, weight gain

  • Tricyclic Antidepressants (TCAs)

    • Many TCA compounds are available

    • Work by inhibiting serotonin and noradrenaline reuptake

    • Tricyclics are non-addictive medications used to treat depression, mood disorders, anxiety, PTSD, OCD and panic attacks

    • TCAs help to maintain neurotransmitters at normal levels

    • Side effects: Weight gain, off-target effects (Alpha adrenoceptors, muscarinic receptors, histamine receptors)

      • Highly dangerous is overdosed

  • SSRIs

    • Inhibit serotonin reuptake

    • Also used to treat panic disorder, OCD, PTSD

    • Antidepressant and anxiolytic effect involves adaptation to chronically elevate brain serotonin…including increase in hippocampal GR

      • Enhanced feedback regulation CRH neurons in hypothalamus → dampened anxiety

    • E.g. Fluoxetine (prozac)

    • Side-effects: Nausea, sexual difficulties and nervousness

• ANS control of the heart

• B-Adrenergic Receptor Antagonists (Beta-Blockers)

  • Stress symptoms, i.e., physiological tremor, tachycardia, nervous sweating and blushing are caused by excessive sympathetic stimulation (excessive catecholamine release)

  • Continuous recording of heart rate in a spectator watching a live football match

  

  • Examples of beta-blockers: Propranolol (non-selective), atenolol (beta-1 selective)

  • Block adrenaline/noradrenaline to access to beta receptors, thus a reduced “fight or flight” reaction

  • Reduce symptoms associated with sympathetic activation: e.g., palpitation (rapid heartbeat), tremor (shaking), blushing and nervous sweating

  • Fast-acting and non-habit forming. Not FDA approved anxiolytics, but are commonly prescribed off-label for anxiety and panic, especially social or performance activity

  • The NIMH has indicated that “a doctor may prescribe a beta-blocker to keep physical symptoms of anxiety under control”

  • Contraindications: asthma, congestive heart failure, diabetes, vascular diabetes, hyperthyroidism and angina

Criteria for choosing stress disorder treatment

• Expected efficacy based on clinical data

• Associated disorders and problems

• Side effects

• Drug interactions

• Compliance and consent

• Accessibility social support (family, accessibility)

<aside> 📌 **SUMMARY:

• HPA, ANS, is altered in stress disorders; PFC deficiency and amygdala hyperdrive

• Adjunct psychotherapy and pharmacotherapy is effective

• Medication for treating comorbid depression and anxiety (majority)

• Beta blockers reduce arousal**

</aside>

Date: June 27, 2024

Topic: Psychology of Stress

Recall

Notes

• Moderate levels of stress can be a good thing → it is not always a bad thing to have a stress response

• Pro-longed stress exposure can be damaging

HPA Axis

Glucocorticoids

• Energy for fight or flight

• Increase vigilance to environmental stimuli

• Enhance emotional learning and memory

• Bind in hippocampus to initiate negative feedback loop

• Extended exposure remodels neurons in stress-sensitive brain regions

Medial Prefrontal Cortex (mPFC)

• Top image is coronal slice from an actual brain

• Grey region is mostly cell bodies and dendrites

PVN (paraventricular nucleus of the hypothalamus)

• Red below

• Starting point of HPA axis

• Has job of responding to life or death changes in our environment

Amygdala

• Darker triangle shape (green) = basolateral nucleus of amygdala

  • Integrates relevant info from environment and tells the central nucleus whether we should be scared

• Lighter area, circle is central nucleus

  • It then relays that information to the hypothalamus and midbrain

Hippocampus

• Provides negative feedback and turns off HPA response

• Present in the last half of the forebrain ; it is very large

Stress and the Brain

• “Pro-Stress” Regions (HPA excitatory)

  • Amygdala

  • Bed Nucleus of the Stria Terminalis (BNST)

• These both promote fear and stress responses ; have the ability to drive activity at the HPA axis

• Commonality between PVN, BNST and amygdala → All express fairly high levels of CRF

  • Main source of CRF in brain in PVN, BNST and central nucleus of amygdala are exception

  • Both of these regions (BNST + amygdala) have high numbers of CRF positive neurons, and when activated, have excitatory effect on fear, anxiety and stress states

• “Anti-Stress” Regions (HPA Inhibitory)

  • Prefrontal Cortex (PFC)

    • Downregulate activity in pro-stress regions like amygdala

  • Hippocampus (HPC)

• Just depends on which area dominates, if amygdala and BNST persist fear can be prolonged

Acute vs Chronic Stress

• Effects of chronic stress

  • HPA axis dysregulation, inflammation, Cardiovascular disease, Gastrointestinal problems, Sexual dysfunction, neurobiological changes

• Experiment 1: Excess glucocorticoid exposure

  • Corticosterone (CORT ; rat version of cortisol) given through drinking water for 20 days

  • Some mice received 1 week washout period

  • CORT exposure destabilises hippocampal (CA1) dendritic structure

    • Causes simplification of basal dendrites in the hippocampus

    • Weakened hippocampus → Bad for regulating stress response

• Experiment 2: Excess Glucocorticoid

  • Decreased dendritic spine density

    • Left these neurons simplified and weakened

  • Orbitofrontal cortex didn’t recover from the “washout” (removal of the stress), it was more sensitive

  • Amygdala is very different, stress exposure made these neurons stronger and more excitable

    • These effects were temporary though

Individual differences in stress responsivity

• Neurobiology

• Genetics

• Age

• Experience

PTSD

• Example: Only 5-10% of trauma-exposed people will develop PTSD

  • Study looked at difference in veterans

  • Those with smaller hippocampal volume were more likely to develop PTSD

  • The volume of the non-combat-exposed twin could predict the likelihood of PTSD for the combat-exposed twin

    • Combat did not shrink the hippocampus, but the size of the hippocampus pre-determined determines the vulnerability to developing PTSD

• Identifying Genetic Differences in PTSD

  • Looking for genetic markers in those who have PTSD compared to those without it

• Grady Trauma Project

  • People participated in small studies as they wait in hospital

  • People who lived in downtown Atlanta were more traumatised than veterans from Iraq

  

• PTSD Genetics

  • PTSD-Associated differences in HPA-related genes

    • FKBP5 - Impacts of sensitivity of glucocorticoid receptors

    • ADCYAP1R1: Impacts release of ACTH from pituitary

    • OXTR: Impacts function of oxytocin receptor

Oxytocin and the HPA Axis

• Oxytocin and CRF expressed in separate neuronal populations in PVN

• Two populations compete for dominance

• Oxytocin is perfectly situated to exert control over our stress response

  • Can lead to dysregulation

• OXTR: People with risk gene that gives them less effective version of oxytocin receptor were more sensitive to effects of trauma

  • Though, genetics are not the only influence → social attachments are a much stronger predictor

• Those with insecure attachment were much more susceptible to trauma, and compounded with the high risk gene there is a huge effect

Age and stress

• Hormonal stress response lasts twice as long in adolescents compared to adults

• Negative feedback not working well in adolescents, they take too long to get back to baseline after a stressor

• Adolescent rats exposed to chronic stress, were unable to suppress fear response to cue after it had been extinguished

Love and Stress

• After they bonded, they separated the rats

• If you depress a rat, they will just float in the water rather than attempting to swim

• Tail suspension test → time spent just accepting defeat and hanging

• HPA Axis and Heartbreak

  • Blocking CRF activity suppresses the effects of “heartbreak”

  • Rats paired with a female, regardless or separation, there is increased CRF in the BNST

<aside> 📌 **SUMMARY:

• The brain can enhance or suppress the HPA stress response

• Chronic stress changes the brain

• Individual differences in neurobiology, genetics, experience and developmental stage can shape stress responsitivity

• Social stress has a profound impact on HPA function**

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