Fear and Anxiety Flashcards
Which receptor is very important in anxiety related disorders?
GABA
What evidence is there for GABA’s role in anxiety disorders?
Patients with panic disorder have less BDP binding sites and lack inhibitory control in cortical and limbic regions to suppress inappropriate fear responses
Which types of drug increase GABA receptor activity?
Agonists; alcohol, barbiturates
Indirect agonists; BDP
What does increased GABA receptor activity do?
Reduces anxiety
What types of drug decrease GABA receptor activity?
Antagonists; flumazenil
Inverse agonists; beta-CCM
What does decreased GABA receptor activity do?
Increases anxiety
What do BDP’s do?
Increase the effectiveness of GABA at opening Cl- channel
Greater influx of chloride and greater hyperpolarisation
What are the effects of diazepam in mice?
Decreased anxiety about a potentially dangerous environment
How do you switch of BDP binding?
By switching the histidine in the N-terminal for arginine
What is the extracellular trail?
It is a protein structure important for BDP binding
What is Kluver-Bucy syndrome?
A malfunction in both the right and left medial temporal lobes
What symptoms are associated with Kluver-Bucy syndrome?
- little or no fear response
- oral and tactile exploration
- hyper sexuality
- bulimia
- inability to recognise objects/faces
What can the effect of bilateral amygdala lesions be?
No fear responses
Where is the amygdala and what does it consist of?
It is found in the temporal lobes and has a complex structure consisting of 22 separate nuclei
What is some evidence for the amygdala’s role in fear?
Activation during public speaking in subjects with social anxiety disorder
Exposure to phobias show activation
High density of BDP
What is anxiety and some of its associated disorders?
An unwarranted or inappropriate fear or stress response
- PTSD
- PD
- GAD
- Phobias
- OCD
What influence does the amygdala have on other brain areas during fear response?
It excites the Locus Coeruleus (releasing noradrenalin) and the Hypothalamus
What is the HPA axis?
Hypothalamus releasing CRH
Pituitary releasing ACTH
Adrenal cortex releasing cortisol
What is activated during the flight or fight response?
Sympathetic nervous system; increased HR, BP, breathing, perspiration…
Central nervous system; behavioural arousal, emotional response
What role does the hippocampus play in fear response?
Lesions can have anxiolytic effects
BDP’s can have direct effects of GABAergic inhibition in hippocampus
Activation of glucocorticoid receptors preventing limitation of cortisol production
What affect does midazolam have when injected into the hippocampus?
Decrease in contextual fear response
What happens in the Locus Coeruleus during fear responses?
Noradrenergic projections onto the cerebellum, hippocampus, neocortex and thalamus
Firing increases during events important for survival
What effect does BDP have on the Locus Coeruleus?
Decreases the release of noradrenaline
What happens in the Raphe nuclei during fear responses?
Serotonergic projections to striatum, nucleus accumbent, frontal cortex and hippocampus
What affect does punishment stimuli have on the Raphe nuclei?
Activation of the serotonergic system leading to behavioural inhibition
What affect does BDP have on the Raphe nuclei?
Decreases serotonin activity
What are some of the causes of anxiety disorders?
Diminished hippocampal activity
Loss of feedback to amygdala
Inappropriate fear responding
What is the noradrenergic system responsible for?
Arousal and attention
What is the serotonin system responsible for?
Mood and emotion
What can dysregulation of the limbic system lead to?
Inappropriate fear and anxiety responses
What are some treatments for anxiety disorders?
BDP’s
Serotonin selective reuptake inhibitors
Buspirone
Which disorders do BDP’s help with?
GAD and PD
Which disorders do SSRI help with?
OCD, PTSD, PD and GAD
What is a drawback of using SSRI’s?
The can have an axiogenic effect for the first few days before becoming anxiolytic
What disorders does Buspirone help with?
GAD
