MODULATING 5HT OR NA IN ANXIETY

What neurotransmitter is strongly implicated in anxiety and panic disorders?

5-HT (serotonin)

Where are 5-HT cell bodies primarily located?

Raphe nuclei

Which brain regions do serotonergic neurons project to in anxiety pathways?

Hippocampus amygdala and prefrontal cortex

What is associated with 5-HT hypofunction?

Environmental hypersensitivity

What is observed in the CSF of GAD patients regarding serotonin?

Reduced 5-HT levels

What does SSRI stand for?

Selective serotonin reuptake inhibitor

What is the main mechanism of SSRIs?

Inhibit serotonin reuptake increasing 5-HT in the synapse

What happens initially when SSRIs increase synaptic serotonin?

Overactivation of presynaptic 5-HT1A autoreceptors

What type of G protein is linked to presynaptic 5-HT1A receptors?

Gi/o

What effect does Gi/o activation have on calcium channels?

Closes calcium channels

What effect does Gi/o activation have on potassium channels?

Opens potassium channels

What effect does activation of presynaptic 5-HT1A receptors have on neurons?

Hyperpolarisation and inhibition

How does presynaptic 5-HT1A activation reduce serotonin release?

Reduced SNARE protein binding and reduced exocytosis

Why can SSRIs initially make anxiety symptoms worse?

Increased serotonin activates inhibitory autoreceptors reducing 5-HT release

Why do SSRIs become effective after chronic use?

Autoreceptors normalise or desensitise increasing serotonin transmission

What anxiety disorders are SSRIs effective in?

GAD phobias and PTSD

How do SSRIs compare to TCAs and MAOIs for side effects?

Lower side effect profile

Why are benzodiazepines sometimes combined with SSRIs initially?

SSRIs have a slow onset of action

What type of drug is buspirone?

5-HT1A partial agonist

What additional receptor action does buspirone have?

D2 antagonist

What is a partial agonist?

A drug with affinity but submaximal efficacy

How does buspirone differ from full serotonin activation?

Produces limited receptor activation and less inhibition

What effect does buspirone have on neuronal firing threshold?

Makes it easier to reach threshold

What anxiety disorder is buspirone mainly effective in?

GAD

What are common side effects of buspirone?

Dizziness nausea and headache

How does the side effect profile of buspirone compare with benzodiazepines?

Better side effect profile

Does buspirone have a rapid or slow onset?

Slow onset

What neurotransmitter is involved in physiological stress and panic responses?

Noradrenaline

What is the major noradrenergic pathway involved in anxiety?

Locus coeruleus NA pathway

What physiological symptoms are mediated by noradrenaline in anxiety?

Tremor palpitations and sweating

What characteristic do NA pathways show in anxiety?

Highly stress sensitive

What can NA pathways become conditioned to?

Fearful stimuli

What class of drugs can reduce the physical symptoms of anxiety?

Beta adrenoceptor antagonists

What is an example of a beta adrenoceptor antagonist used in anxiety?

Propranolol

What symptoms of anxiety can propranolol treat?

Tremor palpitations and sweating