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Flashcards in Fear and Anxiety Deck (16):
1

Evidence of GABAergic dysfunction in anxiety disorders?

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

2

Drugs increasing GABAA receptor activity reduce anxiety (anxiolytic)

Agonists: Alcohol, Barbiturates
Indirect agonist: Benzodiazepines

3

Drugs decreasing GABAA receptor activity increase anxiety (anxiogenic)

Antagonist: Flumazenil
Inverse agonist: beta-CCM

4

Benzodiazepines (BZDs)

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

5

Benzodiazepine binding GABAA receptor distribution
in mouse brain

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

6

Animal models for studying anxiety

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

7

Kluver-Bucy Syndrome:

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

8

Amygdala and fear

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

9

Benzodiazepines (BZD) and the amygdala

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.

10

Anxiety Disorders

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

11

HPA Axis and Stress

Amygdala excites locus coeruleus + hypothalamus.

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

Locus Coeruleus (LC)
releases noradrenaline

12

Situations of chronic stress in the amygdala

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

13

Locus Coeruleus

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

14

Raphe nuclei

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.

15

Fight or flight or freezing

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

16

The serotonergic system and anxiety

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