Transcript Anxiogenic and aversive effects of CRF in the BNST in the

ANXIOGENIC AND AVERSIVE
EFFECTS OF CRF IN THE BNST IN
THE RAT: ROLE OF CRF RECEPTOR
SUBTYPES
M.F. Olive et al
BNST
Mediates behavioral and autonomic responses to
stressors
 Stimulation > behavioral/endocrine changes
similar to those brought on by stress
 Inhibition > decreased response to conditioned
and/or unconditioned stimulus

Also see increase in learned despair with lesions and
uncontrollable stress
 Coping mechanism?

amygdala
Hypothalamus PVN
CRF
CRF
CRF
Pituitary
ACTH
Adrenal
Glucocorticoids
Systemic
Circulation
BNST
CRF = neurotransmitter
CRF1 = receptor
CRF2 = receptor
May (and often do) have different functions
AIMS
IntraBNST administration of CRF > stress
response
 There are CRF1 and CRF2 receptors in the BNST

What is the roll of each of these receptors?
 Let’s see what happens when we shut one of them
down with an antagonist
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SPECIFICS

Long-Evans (250-300g)

handled
Stress study while they should be
asleep!
 BNST Cannulated
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CRF1 antagonist
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Bilateral
FITC labeled CRF to check placement
390 to 4700mw
habituation
CP154526
CRF2 antagonist

Antisauvagine-30 (AS-30)
TIME LINE
5 days
≥ 1 week
ELEVATED PLUS MAZE (EPM)
EPM
5 days
1 hour
5 min
10 min
CONDITIONED PLACE PREFERENCE (CPP)
CPP
Pairing of drug
w/chamber days1-6
Testing
Day 8
≥ 1 week
CPP testing
CP154,526 = CRF1 antagonist
AS30 = CRF2 antagonist
EPM
CRF with and without
antagonist
CP154,526 = CRF1 antagonist
AS30 = CRF2 antagonist
EPM
Antagonist alone
CP154,526 = CRF1 antagonist
AS30 = CRF2 antagonist
CPP
DISCUSSION
Intra-BNST administration of CRF axiogenic
effects
 Under basal levels of CRF neither antagonist
effects anxiety
 No caged controls

Affects
performance
on EPM
Affects
performance
in CPP
Affects
Unconditioned
anxiety
Affects
Conditioned
Aversive
Learning
ELEVATED PLUS MAZE VS. CONDITIONED
PLACE PREFERENCE

CRF1 is responsible for the anxiogenic effects of
CRF
CRF has a higher affinity for CRF1
 More CRF1 then CRF2 in BNST
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Other studies show that CRF2 does mediate stress to a
degree
 These
o
studies are nonspecific (icv, genetic knockout)
Not remembering vs not acting on bad memories
o
CRF 1 + 2 both increase hippocampal LTP
THAT MEDICAL STUFF
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Chronic stress elevates CRF levels in the BNST
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Excititory inputs from:
Amygdala
 Ventral subiculum
 Limbic cortices
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Was 1 nano mole a physiological dose simulating a
stressor?
Hallmarks of PTSD
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Anxiety
Avoidance of people, objects or places associated