Stress

Question 1

Where does the stress response start in the brain?

Answer 1

The amygdala starts the stress response, when the HPA axis is activated, cortisol inhibits the APA axis

Question 2

What happens with the amygdala in chronically stressed animals?

Answer 2

In animals that are chronically stressed, the amygdala is more active and thus actives the HPA axis more

Question 3

How does the amygdala start the stress response?

Answer 3

In the prescence of a stressor, the amygdala excited the hypothamlamus, causing the release of CRH into the hypothalamic-pituitary portal system

Question 4

Is the pituitary gland brain tissue?

Answer 4

Posterior pituitary is neural tissue, anterior pituitary is not brain tissue

Question 5

How is CRH made and where does it travel?

Answer 5

Parvocellular cells produce CRH, then they travel to the anterior pituitary where ACTH is released into the bloodstream (all bloodborne)

Question 6

What does ACTH do when released?

Answer 6

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.

Question 7

What asseses whether something is a stressor or not?

Answer 7

Pre-frontal cortex/anterior cingulate cortex

Question 8

The locus coeruleus is activated by _____

Answer 8

The locus coeruleus is activated by the amygdala, the hypothalamus, the cingulate gyrus, and the prefrontal cortex.

Question 9

What are the effects of LC activation?

Answer 9

LC activation causes norepinephrine release throughout the brain, increasing the excitability o neurons and thus facilitating information processing throughout the brain

Question 10

Difference between epinephrine and norepinephrine

Answer 10

Epinephrine increased activity in the body. Norepinephrine increases activity in the brain.

Question 11

What causes the release of adrenaline?

Answer 11

Epinephrine (adrenaline) is released into the general circulation; the medulla of the adrenal glands, causes this release.

Question 12

What happens to the hippocampus after a stressor?

Answer 12

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.

Question 13

How is the hippocampus related to the HPA axis?

Answer 13

The hippocampus is ONE of the breaks for the HPA axis

Question 14

Chronic stress _______ in the hippocampus.

Answer 14

decreases neurogenesis

Question 15

What is dexamethasone?

Answer 15

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.

Question 16

Benzodiazapine vs Barbituates

Answer 16

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

Question 17

Benzodiazepines Pharmacokinetics:

Answer 17

administered orally, IM, IV, or via mucosal membranes. Highly lipid soluble, effective within 10-15 min; can have a lot of depot binding.

Question 18

Benzodiazepines Metabolism

Answer 18

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.

Question 19

Benzodiazapine Pharmacodynamics

Answer 19

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.

Question 20

Prozac

Answer 20

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

Question 21

Buspirone

Answer 21

directly activates 5HT-1A receptors - have startup

Question 22

Why do anti-anxiety drugs have startup?

Answer 22

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.

Question 23

benzodiazapines; how do they help anxiety in relation to LC?

Answer 23

Benzodiazapines enhance the inhibitory function of GABA on LC neurons.

Question 24

How does CRF interact with LC?

Answer 24

CRF increases anxiety and has an excitatory effect on LC neurons.

Question 25

How do SSRI’s interact with the LC?

Answer 25

SSRI reuptake blockade of 5-HT enhances 5-HT inhibition of LC neurons.

Question 26

How do tryciclyc-antidepressants and MAOIs interact with the LC?

Answer 26

TCAs and MAOIs enhance NE action at inhibitory autoreceptors to reduce LC firing.

Question 27

Two novel treaments for anxiety

Answer 27

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.