L5: Neurotransmission: Anxiety Flashcards
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?
- 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
- Barbiturates: mephobarbital
- Benzodiazepines: Valium
- 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?
SSRI
- 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?
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
Which neurotransmitter system does benzodiazepine selectively act on?
GABA
Describe the basic transference of information on the GABA neurotransmitter system
- GABA within vesicles in the pre-synaptic terminal
- Depolarisation results in the release of GABA
- this will act on GABA receptors on the post-synaptic receptors - 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?
- NA+ enters - in response to mild depolarisation
- causes axon to depolarise
= AP as more positive (-55V) - K+ leaves
- action repolarises (-70) - 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?
Behavioural:
- hoped for increased alertness/ cognitive enhancers
- Got: lots of fear sensations
Useful?
- 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?
- GABA-A receptors
- ionotropic receptor (membrane bound)
- composed of 5 units
- Considerable variety in the detailed sub-unit structures - 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?
- Rats conditioned to fear a tone after pairing tone and foot shock
- Tone alone = increase in blood pressure + freezing
- Conditioning process greatly reduced when the amygdala in rats was damaged
