L5: Neurotransmission: Anxiety Flashcards Preview

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Flashcards in L5: Neurotransmission: Anxiety Deck (40)
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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


What are the 2 main symptoms of clinical anxiety?

1. Fear
2. Worry


How does fear manifest in someone with clinical anxiety?

- panic
- phobia


How does worry manifest in someone with clinical anxiety?

- Anxious misery
- apprehensive
- expectation
- obsessions


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

NICE - mostly based around behavioural treatments


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


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


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


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

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


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

- suggests drugs restore normal function of the brain

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


Which neurotransmitter system does benzodiazepine selectively act on?



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


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

- re-uptake
- breakdown


What is a receptor constructed from?

a series of subunits - proteins


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)


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

- Alcohol
- Barbiturates


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


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


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


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

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

- military: enhanced interrogation technique


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


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

mouse brain:
- White + yellow = highest densities

= hippocampus
= amygdala

= + related structures


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


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


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)


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


What is noradrenaline?

- peripheral stress hormone
- central neurotransmitter


What does the Locus coeruleus (hindbrain) contain?

- noradrenergic cell bodies
- sub-cortical structures including amygdala


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?


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