anxiogenic and aversive effects of crf in the bnst in the rat: role of crf receptor subtypes
DESCRIPTION
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 - PowerPoint PPT PresentationTRANSCRIPT
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?
Hypothalamus - PVN
Pituitary
Adrenal
Systemic Circulation
amygdala
BNST
CRFCRF
CRF
ACTH
Glucocorticoids
CRF = neurotransmitterCRF1 = receptorCRF2 = 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
SPECIFICS
Long-Evans (250-300g) handled
Stress study while they should be asleep!
BNST Cannulated Bilateral FITC labeled CRF to check placement 390 to 4700mw habituation
CRF1 antagonist CP154526
CRF2 antagonist Antisauvagine-30 (AS-30)
TIME LINE
Cannula
tio
nEPM
test
ing
5 days
≥ 1 week
CPP te
stin
g
ELEVATED PLUS MAZE (EPM)
Cannula
tio
nEPM
test
ing
5 days
1 hourhabituate
dinjection
Elevated
plus maze
5 min 10 min
EPM
CONDITIONED PLACE PREFERENCE (CPP)
CPP
EPM te
stin
g
≥ 1 week
Pairing of drug w/chamber days1-6
Testing Day 8
CPP testing
EPM
CP154,526 = CRF1 antagonist
AS30 = CRF2 antagonist
CRF with and without antagonist
EPM
CP154,526 = CRF1 antagonist
AS30 = CRF2 antagonist
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 performanc
e in CPP
Affects Unconditione
d 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
Other studies show that CRF2 does mediate stress to a degree
These studies are nonspecific (icv, genetic knockout)
o Not remembering vs not acting on bad memories
o CRF 1 + 2 both increase hippocampal LTP
THAT MEDICAL STUFF
Chronic stress elevates CRF levels in the BNST Excititory inputs from:
Amygdala Ventral subiculum Limbic cortices
Was 1 nano mole a physiological dose simulating a stressor?
Hallmarks of PTSD Anxiety Avoidance of people, objects or places
associated