Flashcards in Fear and Anxiety Deck (16):
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
Drugs increasing GABAA receptor activity reduce anxiety (anxiolytic)
Agonists: Alcohol, Barbiturates
Indirect agonist: Benzodiazepines
Drugs decreasing GABAA receptor activity increase anxiety (anxiogenic)
Inverse agonist: beta-CCM
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
Benzodiazepine binding GABAA receptor distribution
in mouse brain
α1 - everywhere
high in cortex
α2 - everywhere (but less)
limbic structures hippocampus, amygdala striatum, spinal cord
α3 - reticular activating structures brain stem basal forebrain, spinal cord
α5 - hippocampus,
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
Disorder that occurs when both the right and left medial temporal lobes of the brain malfunction.
Amygdala and fear
Conditioned fear: The association of a neutral stimulus with a fear-inducing stimulus leads to the neutral stimulus becoming fearful.
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.
Post traumatic stress disorder (PTSD)
Panic disorder (PD)
Generalized anxiety disorder (GAD)
Obsessive Compulsive Disorder (OCD)
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)
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
Noradrenergic projections to cerebellum, hippocampus, neocortex and thalamus. Benzodiazepines decrease the release of noradrenaline in the LC
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.
Fight or flight or freezing
Anxiety associated with arousal - Mediated by brain noradrenergic systems
Anxiety associated with behavioural inhibition - Mediated by brain serotonergic systems