Fear and Anxiety

Question 1

Evidence of GABAergic dysfunction in anxiety disorders?

Answer 1

Patients with Panic Disorder have less benzodiazepine binding sites. Patients with panic disorders show far fewer benzodiazepine binding sites, so they are less responsive to GABA’s inhibitory signals so the brain will be more excitable

Question 2

Drugs increasing GABAA receptor activity reduce anxiety (anxiolytic)

Answer 2

Agonists: Alcohol, Barbiturates

Indirect agonist: Benzodiazepines

Question 3

Drugs decreasing GABAA receptor activity increase anxiety (anxiogenic)

Answer 3

Antagonist: Flumazenil

Inverse agonist: beta-CCM

Question 4

Benzodiazepines (BZDs)

Answer 4

BZD’s binds to a certain subtype
most effective anti anxiety drug
only acts when GABA is binding, if there is no GABA the BZD won’t work

Question 5

Benzodiazepine binding GABAA receptor distribution

in mouse brain

Answer 5

α1 - everywhere
high in cortex
(60% brain)

α2 - everywhere (but less)
limbic structures hippocampus, amygdala striatum, spinal cord

α3 - reticular activating structures brain stem basal forebrain, spinal cord

α5 - hippocampus,
spinal cord

Question 6

Animal models for studying anxiety

Answer 6

A - control animal
Diazepam - show less anxiety like behaviour because they spend time exploring the open arms rather than just being in the closed one

you could only test the mice once because if they go on the maze a second time they might feel more confident about it, so they can only test the mice once

Question 7

Kluver-Bucy Syndrome:

Answer 7

Disorder that occurs when both the right and left medial temporal lobes of the brain malfunction.

Question 8

Amygdala and fear

Answer 8

Conditioned fear: The association of a neutral stimulus with a fear-inducing stimulus leads to the neutral stimulus becoming fearful.

Question 9

Benzodiazepines (BZD) and the amygdala

Answer 9

High density of BZD binding sites in amygdala.
Injection of soluble BZD into amygdala induces an anxiolytic effect in rats.
Injection of a BZD antagonist into amygdala abolishes anxiolytic effect of a benzodiazepine given systemically.

Question 10

Anxiety Disorders

Answer 10

Post traumatic stress disorder (PTSD)
Panic disorder (PD)
Generalized anxiety disorder (GAD)
Phobias
Obsessive Compulsive Disorder (OCD)

Question 11

HPA Axis and Stress

Answer 11

Amygdala excites locus coeruleus + hypothalamus.

Hypothalamus releases CRH
Pituatary releases ACTH
Adrenal cortex releases cortisol
(stress hormone) and adrenaline

Locus Coeruleus (LC)
releases noradrenaline

Question 12

Situations of chronic stress in the amygdala

Answer 12

Chronic activation of glucocorticoid receptors in hippocamus
- increased Ca2+ entry into neurons

	- too much Ca2+  - excitotoxic - cells die  Hippocampus can’t feedback to limit cortisol production

Question 13

Locus Coeruleus

Answer 13

Noradrenergic projections to cerebellum, hippocampus, neocortex and thalamus. Benzodiazepines decrease the release of noradrenaline in the LC

Question 14

Raphe nuclei

Answer 14

Serotonergic projections to striatum, nucleus accumbens, frontal cortex and hippocampus.Benzodiazepines decrease the serotonergic activity in the raphe nuclei.
Increase in social interaction (anxiolytic effect) following administration of midazolam directly into in the raphe nuclei.

Question 15

Fight or flight or freezing

Answer 15

Anxiety associated with arousal - Mediated by brain noradrenergic systems
Anxiety associated with behavioural inhibition - Mediated by brain serotonergic systems

Question 16

The serotonergic system and anxiety

Answer 16

SSRIs (e.g. fluoxetine/Prozac)
-Selective serotonin
reuptake inhibitorsSSRIs prolong action of
5-HT in the synapse