HMB200H1 Lecture Notes - Lecture 17: Reticular Formation, Orbitofrontal Cortex, Hand Washing

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17 Mar 2012
HMB200H1S L17; March. 13, 2012
Mental Disorders & Limbic Systems
All seem to involve amygdala disruptions
Fear learning seems to occur in lateral & basal lateral amygala, then
descending paths to hypothal & brainstem
Fear experiences influenced by context, surrounding circumstances,
info from hippocampus
Fear treated by many drugs
Pharmacology of Fear & Anxiety
Fear inhibited by benzodiazepines/tranquilizers (GABAa agonists
in central/output amygdala) on cannabis recs (CB1
endocannabinoid recs in lateral & basolateral amygdala for fear
conditioning, also found on CCK interneurons in amygdala) in
o Ex. give before surgery, then don’t need anesthesia
o Get thru surgery w/o uncomfortable side effects
o Activate inhibitory GABAa recs
o Useful in shorterm since addictive
o Cannabis: feel more relaxed, less anxious about circumstances
(ethanol has similar effects)
Fear very much dependent on activation of amygdala
Fear activated by NMDA or CCKb agonists in amygdala.
o NMDA glutamate rec activation for turning on fear
o CCK as a peptide makes panic attack in humans blocking
blocks panic attacks but not endogenous panic attacks
o When inject CCK-like peptides into amygdala of animals (incl.
Rats) panic-like effects
o Prevent systemic & amygdala effects of CCK by using CCKb rec
Stress/anxiety activated by CRH in BNST.
o Corticotropin releasing hormone, also produced in amygdala
goes to recs in extended amygdala
Peripheral effects of stress hormones (CRHACTHcortisol) and
central effects on limbic system.
o Central? stress hormones via hypothal-pit-adrenal axis
o Central effects also on limbic system w central CRH recs
central anxiety effects
o CRH produced in hypothal
Anxiety Disorders I amygdala changes
Large spectrum
Specific fears, often learned by experience
o 1 trial pavlovian fear conditioning
o Ex. fear of spiders due to spider bite
o Can become disabling if too strong
Usually easily treated by psychotherapy “progressive
desensitization” aka extinction therapy
o Ask what situations afraid of spiders; talk about in safe situation,
read books about them, talk about them, learn some aren’t even
o Learn fear doesn’t have to generalize at all spiders; go to zoo,
play w fake spiders (ex. green then black), gradually become
desensitzed to words+pictures+names handle real spiders,
realize rational
o Progressive exposure in safe envt more adventurous, safe,
happy w those situations
Panic attacks:
Severe sympathetic overreactions to uncomfortable situations.
o Usually involve debilitating theory such a severe reaction that
the thought activates severe sympathetic overreaction
Can lead to agoraphobia not wanting to go out
o Can lead to no longer wanting to fn in normal social situations
Often related to specific fears but become more generalized to
wider range of situations
o Need thought therapy and tranquilizers to actually face fears,
experience more, then overcome panic attacks
o Usually treated w tranquillizers & psychotherapy. Amygdala?
Can be induced by CCK, amygdala stimulation (eps in animals)
Work on learning of fear within amygdala circuits
Post-traumatic stress (used to be called shell shock):
Fear brought on by specific trauma, e.g., violence or accident.
o Very often in ppl w near-death experiences, violent attacks,
accidents longterm PTS
Nightmares reliving experience, fear related to situations
o Debilitating to normal sleep, emotional adaptations don’t
want relationships w ppl that remind them of events
o Don’t want to talk to family, can last for years
Unable to perform normal duties after WW1
o Many students died, 25-40% of front-line soldiers unable to
o After WW1, psych department at UofT converted from bhvr’al
department to treating shell-shock victims
o 25% of current soldiers coming from Afghanistan have PTSD,
millions of dollars spent by CA & USA
Trying to combine psychotherapy & tranquilizers
o Extinction therapy more targeted to amygdala than just
GABAa recs
o Reconsolidation: Most effective
Give tranquilizer, bring back to situation
Revive experience, make seem less frightening find out if
can get experience removed by reliving
Ex. Computer goggles to relive visually more positive than
thru nightmares (which makes worse)
Drugs removing learning of amygdala
Generalized anxiety:
Persistent worries & discomfort with life
o CCK gaba neurons have effect upstream for gaba-gaba
disinhibition (inhibit inhibitions of central nucleus) don’t have
to know
o GABA neurons can effect each other
o Generalized anxiety: sort of dif category
o General fearfulness about the world
o Don’t have just one phobia or specific experience
o Persistant worries about whole life experience & adjustment
Lots of comorbidity, esp w depression
o Closely associated w depression & families
o Comorbidity (overlapping populations, ex. drug comorbidity w
depression) ppl w psychological problems tend to have many
psychological problems
o More biological condition, tend to have parents that have
suffered w depression or generalized discomfort w world
Treated w SSRIs or tranquillizers.
o Can’t just treat w psychotherapy since so generalized; so tend
to treat w SSRIs (slower, long-term treatment,
Post-Traumatic Stress Disorder
First have flashbacks, intrusive memories
Fear someone will come after them more fear
Face contorts w fear due to loud noise hypervigilant (easily
affected, startle response higher)
Anxiety Disorders II -
More involve striatal changes than amygdala changes
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