stress response systems
two simultaneous response systems
sympathetic nervous system: fight or flight
HPA axis: CRH stimulate the secretion of ACTH, which stimulate the secretion of cortisol. Cortisol binding to the glucocorticoid receptor shuts off the stress response system, but chronic binding desensitizes receptor
corticosterone (CORT)
the major stress hormone secreted from the adrenal glands during real or perceived threat;
chronic CORT & stress induce persistent depressive-like behavior: anhedonic-like behavior (sucrose consumption can be used to model anhedonia in rodents), rigid perseverative decision-making, diminished motivation
experiment: habits are insensitive to changes in the relationship between actions and their outcomes
reinforced response vs degraded response
choice test
stressor is corticosterone
corticosterone along is sufficient to replicate this effect
experiment: progressive ratio conditions
decreased BDNF with less response
local BDNF infusion reverses corticosterone-induced phenotype
hippocampal BDNF is essential for the antidepressant effects of classical antidepressants; stressor exposure reduces hippocampal BDNF
stressor exposure
exposed to the stressor remodeling the dendrites;
dendrite arbor of CA3 neurons of subordinate decreases;
dendritic remodeling to stressor is dynamic;
prolonged stressor exposure
CRH in hypothalamus and cortisol in adrenal gland increases;
desensitization and a failure in negative feedback
anxiety is associated with CRH systems
anxiety = prolonged response to potential threat
CRH is elevated in depression and chronic anxiety;
CRH receptor antagonists are being tested for their utility as anti-anxiety drugs;
these compounds may also have utility in the treatment of addictive-like behaviors by reducing the ‘stress’ associated with opioid withdrawal
assess anxiety-like behavior in rodents