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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 SPECIFICS Long-Evans (250-300g) handled Stress study while they should be asleep! BNST Cannulated CRF1 antagonist 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 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 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