Following a major stressor, mixed symptoms of anxiety and depression
Obsessive thoughts, compulsive behaviors
Egodystonic: thoughts/behaviors in conflict with the ego (people with OCD know obsessions/compulsions are irrational but they do it anyway)
Key brain structure related to anxiety disorders
Amygdala and the HPA axis
Amygdala activates the hypothalamus, releases CRF to initiate HPA stress response (stimulates pituitary, releases ACTH, stimulates adrenal gland to release cortisol), increasing plasma cortisol
Cortisol stimulates hippocampus, which has inhibitory effect on HPA axis to prevent excessive cortisol release
Dual role of CRF
CRF released by hypothalamus to act on pituitary gland to control release of glucocorticoids from adrenal cortex in response to stress (HPA axis)
CRF also acts as a neurotransmitter in brain areas associated with anxiety and is released following threatening stimuli, causing behavioral signs of anxiety and altered autonomic nervous system function
Drug effects on locus coeruleus cell firing (BDZs, SSRIs, TCAs, MAO-Is)
CRF increases anxiety and has an excitatory effect on LC neurons
BDZs: enhance inhibitory function of GABA on LC neurons
SSRIs: reuptake blockate of 5-HT enhances 5-HT inhibition of LC neurons
TCAs and MAO-Is: enhance NE action at inhibitory autoreceptors to reduce LC firing
Chronic treatment vs. Acute treatment of anxiety
Chronic treatment: BDZs or SSRIs
Acute treatment: BDZs
What is used for acute treatment of anxiety?
GABA-A receptor is (ionotropic/metabotropic); GABA-B receptor is (ionotropic/metabotropic). Which do we focus more on in class?
Ionotropic; metabotropic; GABA-A
Cycling of GABA between glutamatergic neurons and astrocytes
After release of GABA, transport into astrocytes
GABA --> glutamate --> glutamine (metabolized by GABA-T)
Glutamine transported to neuron
Glutamine --> glutamate --> GABA
GABA-A receptors allow the flow of _______ ions
GABA-A receptor has ______ subunits. Name them.
2 alpha, 2 beta, 1 gamma or delta
BDZ binding site on GABA-A receptor when.....
Alpha subunit next to a gamma subunit
BDZ binding on GABA-A receptors: What's going on?
Nothing happens in absence of GABA
When BDZ is bound, GABA becomes more potent (more chloride allowed in)
Major actions of benzodiazepines
Sleep (soporific effect)
Seizure treatment with valium
Treat seizure with valium to break the seizure, then a longer-lasting anticonvulsant to keep the patient seizure-free (this is because valium will get to work quickly)
Subtypes of the alpha subunits on the GABA-A receptor and what they're associated with
Alpha-2: Anxiolytic and muscle-relaxant
Inverse agonists of BDZs ________ the flow of chloride in the GABA receptor channel and lead to _________ anxiety.