Exam 4: Anxiety Part 2 Flashcards
hormones and neurotransmitters involved in anxiety (5)
- CRF (cortisol)
- NE
- GABA
- Serotonin
- Dopamine
Corticotropin releasing factor (CRF)
- released from hypothalamus in response to stress
- CRF causes anterior pituitary to release ACTH which releases glucocorticoids like cortisol from adrenal cortex
neurochemistry of CRF - normal person
- glucocorticoids induce changes to adapt to environmental challenges
- inc blood sugar, inc BP
- reduces inflammation/immune response
- mobilizes resources and energy in response to immediate environmental challenge
high cortisol acts as negative feedback to HPA system to bring cortisol levels down to normal
CRF interacts with brain regions - anxiety
CRF acts as a ____
CRF neurons originate in amygdala and project to locus coeruleus (NE center of brain) and activate adrenergic component of stress response
CRF release starts to activate arousal networks, inc vigilance
CRF acts as a neurotransmitter
Norepinephrine
released at target visceral organs in sympathetic activation
prepares response to danger
NE and epi are important in formation of emotional memories!!!
high NE helps remember that something was a threat
what impairs the formation of emotional memories
B-adrenergic antagonists
-propranolol - modifies BP - blocks NE B receptor preventing memory to underly long term causes of PTSD
NE and anxiety evidence (4)
-associated with inc activity in locus coeruleus - hyperarousal, hypervigilant
-a2-autoreceptor antagonist Yohimbine can produce panic attacks in PTSD
drugs blocking autoreceptor inhibit further NE release, disinhibiting LC can inc panic attacks
- they have abnormal autonomic nervous system activity - dramatic responses to neg stimuli
- veterans with PTSD have higher than normal NE levels
LC projects to ____ that has roles in attention and working memory
PFC
activation of a2 autoreceptor in PFC
enhances working memory
activation of a1 receptors (excitatory)
deleterious effect on cognitive functions
-overstimulated and now you cannot focus or concentrate
for a normal person NE has a higher affinity for what receptors in the PFC
a2 receptors
In cases of inc NE, under stress or anxiety what receptor activation is inc
a1 receptor activation inc which can lead to cognitive impairment
GABA
gltamatergic neurons from PFC stimulate GABA in the amygdala
-if threat PFC says do not worry and activates GABA
GABA and anxiety
impaired GABA function - overactive amygdala activity
glutamate sends to GABA to stop but it cannot - indicating an aversive event
where are GABA receptors found in high concentrations (3 areas)
amygdala, limbic system, cerebral cortex)
what happens when you walk into a test and you realize you studied for the wrong thing - no PFC
amygdala - omg there is an exam
activates hypothalamus: inc HR
activate brainstem : muscles, tingly, shaky - sympathetic activation, stress response
GABA A receptors
ionotropic
Cl- channels open and Cl- enters cell, hyperpolarizing it - dec amount of action potentials
benzodiazepines and barbiturates and GABA
they cause sedation and reduce anxiety by binding to allosteric sites on the receptor complex
what do patients with panic disorder show on PET scans in relation to benzodiazepines
dec benzodiazepine binding in the CNS - mainly frontal lobes
less binding sites can result in failure of GABA to inhibit resulting in uncontrolled panic attacks, phobias, hyperarousal of PTSD, generalized anxiety
serotonin and anxiety
there is a sweet spot between to little and too much serotonin
inc serotonin can worsen anxiety
-inability to control stressor increases activity in the dorsal raphe nucleus!!
what serotonin receptor is involved in anxiety
5-HT1A
5-HT1A injection in hippocampus or amygdala
receptor is postsynaptically
anxious behaviors increase
5-HT1A injection into raphe nuclei
receptors somatodendritic autoreceptors
anxiolytic effect occurs
individuals with anxiety show reduced 5-HT1A binding _____
in the raphe
less ability to shut down the serotonin raphe mediated response so you will release more serotonin than needed
first line of treatment for anxiety
SSRIs
SSRIs what do they do
acutely block reuptake of serotonin - prolonging its effects
- it initially inc anxiety which is why some may stop taking it
- long-term neuronal adaptations are required for its effectiveness - altered pharmacodynamic sensitivity
mesocortical DA projects to
VTA and mPFC
anxiety and dopamine
stress inc firing of mesocortical DA neurons, inc DA turnover in PFC
-more DA broken down in cortex
reducing DA transmission with lesions of VTA … amygdala___
amygdala pathway reduces conditioned fear response and impairs acquisition of avoidance behavior
injections of D1 receptor agonists vs D1 antagonists
D1 agonists: inc anxiety
D1 antagonists: produce anxiolytic effects
stress initiating phasic burst firing of DA into NAcc
chronic activation when threat is no longer present predicts vulnerability to dysfunctional responses in social interactions in SAD
stressor will feel rewarding -good initially to notice things that are bad - helps you survive
