Stress Flashcards
Where does the stress response start in the brain?
The amygdala starts the stress response, when the HPA axis is activated, cortisol inhibits the APA axis
What happens with the amygdala in chronically stressed animals?
In animals that are chronically stressed, the amygdala is more active and thus actives the HPA axis more
How does the amygdala start the stress response?
In the prescence of a stressor, the amygdala excited the hypothamlamus, causing the release of CRH into the hypothalamic-pituitary portal system
Is the pituitary gland brain tissue?
Posterior pituitary is neural tissue, anterior pituitary is not brain tissue
How is CRH made and where does it travel?
Parvocellular cells produce CRH, then they travel to the anterior pituitary where ACTH is released into the bloodstream (all bloodborne)
What does ACTH do when released?
ACTH from the anterior pituitary leads to corticol release from cortex of the adrenal glands; cortisol is one of the signatures of the body’s stress response.
What asseses whether something is a stressor or not?
Pre-frontal cortex/anterior cingulate cortex
The locus coeruleus is activated by _____
The locus coeruleus is activated by the amygdala, the hypothalamus, the cingulate gyrus, and the prefrontal cortex.
What are the effects of LC activation?
LC activation causes norepinephrine release throughout the brain, increasing the excitability o neurons and thus facilitating information processing throughout the brain
Difference between epinephrine and norepinephrine
Epinephrine increased activity in the body. Norepinephrine increases activity in the brain.
What causes the release of adrenaline?
Epinephrine (adrenaline) is released into the general circulation; the medulla of the adrenal glands, causes this release.
What happens to the hippocampus after a stressor?
The hippocampus is excited by elevations in cortisol, NE, and glutamatergic inputs from throughout the brain
It projects to the hypothalamus and activates GABA neurons there, which decrease hypothalamic activity.
How is the hippocampus related to the HPA axis?
The hippocampus is ONE of the breaks for the HPA axis
Chronic stress _______ in the hippocampus.
decreases neurogenesis
What is dexamethasone?
Dexamethasone is a corticosteroid that can be administered. When you give a normal person the dexamethasone, their cortisol level goes down.
When you give an anxious/depressed person the dexamethasone, their cortisol level stays the same.
Benzodiazapine vs Barbituates
Benzodiazepine and barbituates are completely different drugs. Barbituates increase the open time, benzodiazepine increase the flutter frequency. Barbituates don’t need GABA, whereas benzodiazapines need GABA to have an effect
Benzodiazepines Pharmacokinetics:
administered orally, IM, IV, or via mucosal membranes. Highly lipid soluble, effective within 10-15 min; can have a lot of depot binding.
Benzodiazepines Metabolism
metabolized in liver by cytochrome P-450 enzymes; 95% excreted in urine; metabolites are also psychoactive. Induction of liver enzymes is limited, so less tolerance and less x-tolerance with other drugs.
Benzodiazapine Pharmacodynamics
potent GABA-A agonist; only effective when GABA is also present, which is why they are very safe drugs (TI of 500)
Act at GABA-A receptors throughout CNS to reduce activity of the amygdala, prefrontal cortex, hippocampus, hypothalamus, brainstem regions involved in ANS (brains response to stress) activity.
Prozac
SSRI, blocks reuptake of 5HT - have startup
First SSRI to be clinically available
Usually administered orally; LOTS of depot binding to blood platelets (not fat); also lipid soluble to gain acess to brain
Half life of 5 days if taken chronically
Buspirone
directly activates 5HT-1A receptors - have startup
Why do anti-anxiety drugs have startup?
The anti-anxiety effects of these drugs take up to 8 weeks to be expressed – this may be due to increased cortisol receptors in the hippocampus or decreased sensitivity of presynaptic autoreceptors on 5-HT neurons themselves.
benzodiazapines; how do they help anxiety in relation to LC?
Benzodiazapines enhance the inhibitory function of GABA on LC neurons.
How does CRF interact with LC?
CRF increases anxiety and has an excitatory effect on LC neurons.
How do SSRI’s interact with the LC?
SSRI reuptake blockade of 5-HT enhances 5-HT inhibition of LC neurons.
How do tryciclyc-antidepressants and MAOIs interact with the LC?
TCAs and MAOIs enhance NE action at inhibitory autoreceptors to reduce LC firing.
Two novel treaments for anxiety
Novel Treatment 1: CRH antagonist reduces neural degeneration caused by stress
Novel Treatment 2: Impairing reconsolidation by administration of NMDA or NE antagonists may reduce the memory for events that produce anxiety; potential theoretical treatment for PTSD.
