L5: Neurotransmission: Anxiety Flashcards Preview

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Flashcards in L5: Neurotransmission: Anxiety Deck (40)
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1

What is the difference between anxiety and clinical anxiety?

Anxiety = feelings of fear with no reasonable external cause
Clinical Anxiety = same + interferes with other activities and prioirities

2

What are the 2 main symptoms of clinical anxiety?

1. Fear
2. Worry

3

How does fear manifest in someone with clinical anxiety?

- panic
- phobia

4

How does worry manifest in someone with clinical anxiety?

- Anxious misery
- apprehensive
- expectation
- obsessions

5

What is the typical treatment given to someone with clinical anxiety?

NICE - mostly based around behavioural treatments

6

Give in order the 'history' of drugs used to tackle clinical anxiety

1. Barbiturates: mephobarbital
2. Benzodiazepines: Valium
3. SSRI - selective serotonin re-uptake inhibitors

7

Why are barbiturates no longer used to treat clinical anxiety since 1960's?

initially thought to be good as it is an effective anxiolytic BUT....
- has low therapeutic index = easy to over dose
- acts in a relatively non-specific way
- induce tolerance + dependence

8

Why are benzodiazepine preferred over barbiturates?

Ben has...
- higher therapeutic index = safer to overdose
- SPECIFIC anxiolytic effect
- used for a range of clinical disorders
- initially thought to not induce dependence but now a major issue in their use

9

Which of the three drugs, barbiturates, benzodiazepine and SSRI, are the first in line for pharmacological treatment for many anxiety disorders?

SSRI
- used in GAD
- do have a delayed onset of action
(NICE guidelines, 2011)

10

Regarding the 2 different models to treating pathology, disease or symptom -centred, what are we hoping to achieve with the use of drugs?

Disease-centred
- suggests drugs restore normal function of the brain

Symptom-centred
- suggests drugs produce specific changes in aspects of mood
- no necessary assumption drugs will reverse some pre-existing neurochemical abnormality

11

Which neurotransmitter system does benzodiazepine selectively act on?

GABA

12

Describe the basic transference of information on the GABA neurotransmitter system

1. GABA within vesicles in the pre-synaptic terminal
2. Depolarisation results in the release of GABA
- this will act on GABA receptors on the post-synaptic receptors
3. Then GABA is transported back into pre-synaptic terms/ adjacent glial cells by the re-uptake pump

13

What are the 2 ways in which a neurotransmitter system can be inactivated?

- re-uptake
- breakdown

14

What is a receptor constructed from?

a series of subunits - proteins

15

What happens when benzodiazepine binds to GABA-A receptors?

Enhances the effect of GABA
- opens a pore in the GABA-A receptor
- allows Cl- to enter (down concentration gradient = keep cell negative)

16

Other than benzodiazepine, what other drug can bind to the GABA-A receptor?

- Alcohol
- Barbiturates

17

Briefly describe how an AP is induced?

1. NA+ enters - in response to mild depolarisation
- causes axon to depolarise
= AP as more positive (-55V)
2. K+ leaves
- action repolarises (-70)
3. Brief hyperpolarising = refractory period

18

How does GABA effect AP?

Inhibitory effect:
- GABA = increases Cl- entering cell = -65mv
- meaning the inside remains more negative so cannot reach the -55V threshold for AP
= GABA impedes depolarisation = making an AP less likely

19

What is the difference in effect when Benzodiazepine binds to just GABA or to GABA-A?

GABA = little enhancement of the GABA effect

GABA-A = greater enhancement of the GABA effect

20

what behaviour effect would you expect if you developed a drug which reduced the effect of GABA at the GABA-A receptor?

Behavioural:
- hoped for increased alertness/ cognitive enhancers
- Got: lots of fear sensations

Useful?
- military: enhanced interrogation technique

21

Describe the GABA-A receptors

Made up of 5 separate subunits
- each is a protein
- coded by a different gene

Subunits are slightly variable in their structure
- altering the sensitivity of the receptor to benzodiazepines

22

In what parts of the brain are benzodiazepine-sensitive GABA-A receptors found?

mouse brain:
- White + yellow = highest densities

= hippocampus
= amygdala

= + related structures

23

What are the 2 major classes of GABA receptor subtypes and their differences?

1. GABA-A receptors
- ionotropic receptor (membrane bound)
- composed of 5 units
- Considerable variety in the detailed sub-unit structures

2. GABA-B receptors
- metabotropic receptor (acts through second messenger)
- works more slowly in a more sustained way

24

What evidence is there suggesting the amygdala is involved in fear - conditioning?

1. Rats conditioned to fear a tone after pairing tone and foot shock
2. Tone alone = increase in blood pressure + freezing
3. Conditioning process greatly reduced when the amygdala in rats was damaged

25

What evidence is there suggesting the amygdala plays a role in processing linguistically coded threat stimuli?

1. ppt asked to name colours of words that are either related to persecution, threat of destruction
2. Fear-relevant words produced greater activation of amygdala (deep within the temporal lobe)

26

What is referred to by the term 'neural circuit of fear'?

- the different parts of the brain affected by the output of the amygdala producing the different aspects of fear

1. Autonomic symptoms
- blood pressure
- heart change
2. Hormonal changes
- increased adrenaline, cortisol
3. Processing of fear-related stimuli

27

What is noradrenaline?

- peripheral stress hormone
- central neurotransmitter

28

What does the Locus coeruleus (hindbrain) contain?

- noradrenergic cell bodies
- sub-cortical structures including amygdala

29

How have noradrenaline been linked to modulating amygdala fear circuits?

LC contains noradrenergic cell bodies

- selective chemogenetic stimulation of these neurons delays the extinction of a simple fear response in rats
-- effect is blocked by propranolol (noradrenergic beta receptor antagonist)

- relevant for PTSD?

30

Why is it suggested benzodiazepines may modulate GABA-ergic inputs to amygdala?

There are many other otential modulators of amygdala function (Serotonin (5HT))
- GABA being one of them and benzo works on GABA