Anxiety

what do cannabinoids cause?

increased firing of the VTA DA neurons

binding to CB1 receptors causes what?

reduced GABA release onto VTA cells

what acts as negative feedback on glutamate release?

endocannabinoid(eCB) 2-AG

how can emotional experiences and learning bypass conscious awareness?

via the thalamo-amygdala pathway

amygdala

can orchestrate a fear response based on input from thalamus (unconscious) or cortex (conscious)

what has the receptors for the glucocorticoid cortisol?

the hippocampus;shuts off stress response

what does stress enhance?

the formation of emotional memories

what treats PTSD?

‘beta-blocker’ propranolol; antagonist for epinephrine and norepinephrine

PTSD

involves the overconsolidation of memory

block of reconsolidation by propranolol

has helped treat PTSD; does not affect declarative memories

kinds of anxiety disorders

generalized anxiety disorder (GAD), panic disorder, agoraphobia, phobias, social anxiety disorder, PTSD, obsessive-compulsive disorder(OCD)

what mediates anxiety?

BNST

what increases dendritic branching in the BNST?

chronic stress

what increases anxiety in people?

acute tryptophan depletion (ATD)

what recudes anxiety-related behaviors in mice?

optogenetic inhibition of BNST

BNST

bed nucleus of the stria terminalis,often considered part of the extended amygdala

how does the amygdala increase arousal and anxiety?

releases CRF into the locus coeruleus

Corticotropin-Releasing Factor (CRF)

stress hormone which activates the HPA Axis

what inhibits the amygdala and thus keeps emotions in check?

the PFC

how does trauma and stress affect the brain?

loss of cells in the PFC and hippocampus; overactive amygdala

how does chronic immobilization stress affect the dendritic branching?

decreases branching in the hippocampus; increases it in the amygdala

drugs used to treat anxiety

positive allosteric modulators; benzodiazepines, barbiturates, ethanol

effects on the conductance of the GABAa receptor

Ro 15-4513 and Ro 19-4603 are inverse agonists

how do benzodiazepines affect GABAa?

increase the # of times the channel opens

How do barbiturates affect GABAa?

increase the duration of the opening

benzodiazepine binding sites

distributed widely, especially in amygdala and frontal cortex

Where do benzodiazepine binding sites have less binding?

less binding(especially in the frontal lobe) in people with anxiety disorders

Therapeutic index(TI)

serves as a measure of drug safety, equals TD50/ED50

what is an acceptable initial therapeutic index for barbiturates?

10-20

what can tryptophan depletion leads to?

an increase in anxiety

the locus coeruleus is the common site of what type of drug?

drugs that reduce anxiety