5- Neurotransmission Flashcards
What is anxiety
A feeling of fear or dread when there is no ‘reasonable’ external cause for anxiety, and fear otherwise.
Clinical anxiety refers to
Anxiety which is ‘pathological’, interfering with other activities and priorities.
Symptoms of anxiety
- Phobia
- Panic
- Anxious misery
- Apprehensive expectation
- Obsessions
Drug Treatment of Anxiety
- Barbiturates
- Benzodiazepines
- Selective serotonin reuptake inhibitors
Selective serotonin reuptake inhibitors
- First line pharmacological treatment (NICE guidelines 2011)
- Used for general Anxiety disorder (GAD)
- They do have a delayed onset of action.
Benzodiazepines
- Evidence for a specific anxiolytic effect
- They are substantially safer than barbiturates in overdose
- Used for a number of other clinical conditions
- Initially thought not to induce dependence however there seems to be an issue
- e.g. Valium
Barbiturates
- have a low therapeutic index
- Act in a relatively non-specific way
- Induce tolerance and dependence
- Clinical use for anxiety ceased in the 1960’s.
A ‘disease-centred’ model for anxiety believes
A drug restores the brain to normal function
A ‘symptom-centred’ model for anxiety believes
Drugs produce specific changes in aspects of mood, motivation and cognition that make a condition, such as clinical anxiety, less disabling
No assumption drugs ‘reverse’ brain to normal
Depolarisation will lead to
GABA release, which will act at the postsynaptic GABA receptors and then be transported back into the presynaptic terminal
What do benzodiazepines do
Enhances the effect of GABA but has ‘no’ effect by itself.
The alpha GABA receptor also has (separate) binding sites for
Alcohol and barbiturates
How many subunits in the alpha GABA receptors are there
5 separate subunits - each is a protein and coded by a different gene
Benzodiazepine-sensitive alpha GABA receptors are selectively expressed higher in which brain areas
The hippocampus, amygdala and related structures.
Two major classes of GABA receptor subtypes
- Alpha GABA (GABAA)
- Beta GABA (GABAB), a metabotrophic receptor – G-protein coupled
Fear-relevant words produce greater activation of
Amygdala
Outputs from the amygdala can modulate different aspects of fear including
- Autonomic symptoms
- Hormonal changes
- Processing of fear-related stimuli
How do those with damage to the amygdala react to fear
Their experience of fear and panic was as great as in the controls who also experienced a panic attack
Complex neural loops run between cortex, striatum and thalamus (CSTC loops) and are responsible for
Modulation of motor output and cognition
Which loop may be responsible for worry and anxiety
Dorsolateral prefrontal cortex (DLFPC)
There is overlap between GAD and
Major depressive disorder (MDD)
Selective serotonin reuptake inhibitors (SSRIs) will enhance
Serotonergic inhibition in both amygala- and CSTC related circuits
Noradrenergic antagonists may reduce noradrenergic inputs which
Can reduce autonomic components of anxiety
Selective serotonin reuptake inhibitors do what
Slow the the removal of serotonin from the synaptic cleft
Buspirone acts as a partial agonist at
Some types of serotonin receptor
Noradrenaline is both
- A peripheral stress hormone
- A central neurotransmitter.
The locus coeruleus (hindbrain) contains
- noradrenergic cell bodies that project forwards to cortex
- Sub-cortical structures including the amygdala.
Selective chemogenetic stimulation of noradrenergic cell bodies does what
Delays the extinction of a simple fear response in rats
What is propranolol
A noradrenergic beta receptor antagonist.
