A NXIOGENIC 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 CRF ACTH Glucocorticoids

CRF = neurotransmitter CRF 1 = receptor CRF 2 = receptor May (and often do) have different functions

A IMS IntraBNST administration of CRF > stress response There are CRF 1 and CRF 2 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 ( g) handled Stress study while they should be asleep! BNST Cannulated Bilateral FITC labeled CRF to check placement 390 to 4700mw habituation CRF 1 antagonist CP CRF 2 antagonist Antisauvagine-30 (AS-30)

T IME L INE Cannulation EPM testing 5 days ≥ 1 week CPP testing

E LEVATED P LUS M AZE (EPM)

Cannulation EPM testing 5 days 1 hour habituated injection Elevated plus maze 5 min 10 min EPM

C ONDITIONED P LACE P REFERENCE (CPP)

CPP EPM testing ≥ 1 week Pairing of drug w/chamber days1-6 Testing Day 8 CPP testing

EPM CP154,526 = CRF 1 antagonist AS30 = CRF 2 antagonist CRF with and without antagonist

EPM CP154,526 = CRF 1 antagonist AS30 = CRF 2 antagonist Antagonist alone

CP154,526 = CRF 1 antagonist AS30 = CRF 2 antagonist CPP

D ISCUSSION 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

E LEVATED P LUS M AZE VS. C ONDITIONED P LACE P REFERENCE CRF 1 is responsible for the anxiogenic effects of CRF CRF has a higher affinity for CRF 1 More CRF 1 then CRF 2 in BNST Other studies show that CRF 2 does mediate stress to a degree These studies are nonspecific (icv, genetic knockout) o Not remembering vs not acting on bad memories o CRF both increase hippocampal LTP

T HAT 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