Fear and Anxiety Flashcards
what are anxiety disorders?
excessive or maladaptive fear response
what are the two areas of the brain that have been found to play a role in fear and anxiety?
the amygdala and the hippocampus
where is the amygdala located?
deep in the temporal lobe
describe evidence that the amygdala is involved in fear
kluver-bucy syndrome is a disorder that occurs when both the right and left medial temporal lobes of the brain malfunction. it results in little to no fear response
describe evidence that the amygdala is involved in anxiety
in participants with social anxiety disorder there is increased amygdala activation when public speaking compared to speaking in private
describe evidence that the hippocampus is involved in anxiety
hippocampal lesions have anxiolytic effects
what part of the nucleus activates fear related behaviour?
the central nucleus
what is the HPA axis?
the hypothalamic pituitary adrenal axis - controls the release of glucocorticoid hormones
which glucocorticoid is involved in anxiety?
cortisol (a stress hormone)
describe the process of the HPA axis
the hypothalamus releases corticotrophin-releasing hormone (CRH)
this stimulates the pituitary gland to secrete adrenocorticotropic hormone (ACTH)
this stimulates the adrenal cortex to release cortisol and adrenaline
describe how the locus coeruleus is involved in anxiety
the LC releases noradrenaline which stimulates the fight or flight response or freeze response
provide evidence that GABAergic disfunction plays a role in anxiety disorders
benzodiazepines are the most effective anxiolytic drug
patients with panic disorder have less benzodiazepine binding sites (PET study with radiolabelled flumazenil - indicating benzodiazepine binding sites)
what is the structure of GABA A receptors?
heteropentameric structure - 5 binding sites
what is the amygdala’s role in anxiety?
sensory information is channelled to the amygdala, the amygdala then excites the hypothalamus and the locus coeruleus
what are drugs that increase GABA A receptor activity called?
anxiolytics - reduce anxiety
what is the difference between a direct and indirect agonist?
direct = binds to the receptor and acts as a neurotransmitter indirect = increases and enhances the amount of neurotransmitters affected but has no effect on the receptor
what are examples of direct and indirect GABA A receptor agonists?
direct = alcohol, barbiturates indirect = benzodiazepines
what are anxiogenic drugs?
drugs that decrease the GABA A receptor activity and increase anxiety
give some examples of antagonist and inverse agonist anxiogenic drugs
antagonist - flumazenil
inverse agonist - beta CCM
what is the difference between antagonists and inverse agonists?
antagonists = bind to receptor and block other molecules from binding, but have no effect on receptor activity
inverse agonists = binds to receptor and has prevents receptor activity
what is the elevated + maze?
a study testing the effects of benzodiazepines in rats. measures an unconditioned response to a potentially dangerous environment
diazepam increases the amount of time spent in the open arms of the maze (less anxiety)
which GABA A receptor subtype is most active in anxiety responses and provide evidence?
alpha 2 subunit knockout mice (with the alpha 2 receptor removed) show more anxiety than the wildtypes (without the receptor removed)
what is the benefit of narrowing down the receptor subtypes that mediate anxiolytic effects?
drugs can be developed that target these subtypes which will produce anxiolytic effects without side effects
where is the highest density of benzodiazepine binding sites?
amygdala
provide evidence for the role of the hippocampus in anxiety responses?
hippocampal lesions have anxiolytic effects, BZ also have a direct effect on the GABAergic inhibition in the hippocampus
what happens in situations of chronic stress?
there is a chronic activation of glucocorticoid receptors in the hippocampus, which results in increased calcium entry into neurons. too much calcium can be excitotoxic, and result in cells dying. this means that the hippocampus can’t feedback to limit cortisol production
what are some causes of anxiety disorders?
diminished activity of hippocampus, loss of feedback to amygdala, inappropriate fear responding
what diffuse modulatory systems also play a role in inappropriate fear and anxiety responses?
noradrenaline (arousal and attention) and serotonin (mood and emotion)
describe how noradrenaline affects the Locus Coeruleus
increased activity of noradrenaline in the LC = increased arousal and attention
how do benzodiazepines affect noradrenaline?
they decrease the release of noradrenaline in the locus coeruleus
what do raphe nuclei do?
produce serotonin
how do benzodiazepines affect serotonin?
they decrease the serotonergic activity in the raphe nuclei
what anxiety response does the noradrenergic system modulate?
arousal - fight or flight
what anxiety response does the serotonergic system modulate?
behavioural inhibition - freezing
