Fear and Anxiety Flashcards
name the difference between fear and anxiety.
fear is a useful and innate response, whereas anxiety is an inappropriate fear response.
give an example of conditioned emotional response.
- mouse trained to lever press for food.
- CS + footshock
- normal levels of lever pressing for food in presence of NS
3b. reduced levels of ever pressing for food in presence of CS.
how many nuclei does the amygdala contain?
22
define the clever-bucy syndrome.
disorder that occurs when both the right an left medial temporal lobes of the brain malfunction.
when amygdala was removed from temporal lobe, what was the outcome?
lack of fear response.
give evidence that amygdala s involved in fear?
- less amygdala leads to less fear
- increased activation during public speaking in subjects with SAD.
- activation following presentation of fearful stimuli.
state the three types of symptoms of anxiety.
emotional = fear cognitive = anxious thoughts somatic = increased heart rate
what parts of the brain does the amygdala activate?
coeruleus and hypothalamus.
describe the HPA axis.
H-hypothalamus releases CRH
P-pituatary releases ACTH
A-adernal cortex releases cortisol and adrenaline
what does lock coeruleus release?
noradrenaline.
name states of sympathetic nervous system.
- increased heart rate
- blood pressure
= prepares brain for situation e.g run faster away from threat
name states of the central nervous system.
- behavioural arrest and arousal
- cortisol activation
describe the role of the GABAergic system in regulating fear/anxiety.
evidence of GABA disfunction in anxiety disorders.
- panic disorder patients have less BZD binding sites.
- panic disorder patients lack sufficient inhibitory control in corticol and limbic regions to suppress inappropriate fear responses.
what occurs in the presence of BZDs as a drug?
- GABA molecules are more effective at opening CL- channel
- greater influx of chloride
- greater hyperpolarisation
- more inhibition
what type of structure do GABAa receptors have?
heteropentameric structure.
state drugs that increase GABAa receptor activity and so reduce anxiety.
- agonists = alcohol and barbiturates
- indirect agonist = BZDs
state drugs that decrease GABAa receptor activity and so increase anxiety.
- antagonist = flumazenil
- inverse agonist = beta-CCM
state side effects of BZDs
- anxiolytic
- anticonvulsant
- sedative
- muscle relaxant
- amnestic
describe what the alpha reactors of BZDs show.
a1 - everywhere high in cortex
a2 -limbic structures, hippocmapus, amygdala
a3 - reticular activating structures brain stem basal forebrain, spinal cord
a4 - hippocampus, spinal cord
describe the elevated and maze study.
- UR to potentially dangerous environment
- anxiety = degree to which animal acids the open arms (less anxious, more confident to explore)
- effect of diazepam = increase in amount of time spent in open arms of the maze.
- drug specific to a2 receptors reduce anxiety as more mice explore open arms!
a suppression ratio of 0 indicates…
an anxious state.
a suppression ratio of 0.5 indicates…
not anxious state.
describe what occurs in the absence of alpha 2 receptors that indicate it is involved in anxiety.
- no difference in acquisition or lever pressing for food before footshock is present
- more anxiety in alpha 2 knockout mice than wildtype when shock is present.
- BZDs reduces suppression in wildtype but not knockout mice.
what type of subunit had no anxiolytic effect?
a2 alpha receptor.
describe the structure of the GABAa receptor.
- protein structure
- 5 protein submits around a central ion (CL- channel), each consists of 4 transmembrane domains.
- extracellular tail
- intracellular loop
where do BZDs bind?
histidine in N-temrinal extracellular domain.
what specific subtype show a good effect?
alpha 1 receptor - causes anxiolytic effect but not sedation.
describe the association between BZDs and the amygdala.
- high density of BZD binding sites in amygdala.
- injection of soluble BZD into amygdala induces an anxiolytic effect
- injection of BZD antagonists not amygdala abolishes anxiolytic of a benzo given systematically.
describe the hippocampus role in anxiety.
- diminished activity of hippocampus can result in anxiety.
- lesions have anxiolytic effects
- Benzos can have a direct effect on GABA inhibition in hippocampus
- decrease in fear response when midazolam is administered to hippocampus
in situations of chronic stress, chronic activation of glucocorticoid receptors in hippocampus leads to…
- increased Ca2+ entry into neurons
- too much Ca2+ = excitotoxic = cells die
name systems what the amygdala and hippocampus respond to.
modulatory systems:
- noradrenergic system = arousal and attention
- serotonin system = mood and emotion
= thought to balance one another.
- deregulation of systems can result in fear and anxiety.
give evidence that the locus coeruleus is involved in anxiety.
- events that are important for survival causes increased firing of LC which increases arousal and attention.
- Benzos decrease the release of noradrenaline in the LC
give evidence that the raphe nuclei is involved in anxiety.
- punishing stimuli activate the serotonergic system which leads to behavioural inhibition.
- benzos decrease the serotonergic activity.
where does the LC project to?
noradrenaline projections to cerebellum, hippocampus, neocortex and thalamus.
where does the raphe nuclei project to?
serotonergic projections to striatum, nucleus accumbens, frontal cortex and hippocampus.
anxiety associated with arousal is mediated by…
brain noradrenergic systems.
anxiety associated with behavioural inhibition is mediated by…
brain serotonergic system.
give common treatments for specific anxiety disorders.
BZDs - GAD and PD
SSRIs - OCD, PTSD, PD, GAD
Buspirone - GAD
SSRIS prolong action of …
5-HT in synapse
describe the function of buspirones.
- 5 HT1A agonist
- somatodendritic receptors
- decrease 5-HT cell firing
- no symptomatic change util weeks int treatment.
