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Anxiogenic and aversive effects of CRF in the BNST in the rat: role of CRF receptor subtypes

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

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Anxiogenic and aversive effects of CRF in the BNST in the rat: role of CRF receptor subtypes

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  1. Anxiogenic and aversive effects of CRF in the BNST in the rat: role of CRF receptor subtypes M.F. Olive et al

  2. 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?

  3. amygdala Hypothalamus - PVN CRF CRF CRF BNST Pituitary ACTH Adrenal Glucocorticoids Systemic Circulation

  4. CRF = neurotransmitter CRF1 = receptor CRF2 = receptor May (and often do) have different functions

  5. 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

  6. 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)

  7. Time Line CPP testing EPM testing Cannulation ≥ 1 week 5 days

  8. Elevated Plus Maze (EPM)

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

  10. Conditioned Place Preference (CPP)

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

  12. CP154,526 = CRF1 antagonist AS30 = CRF2 antagonist EPM CRF with and without antagonist

  13. CP154,526 = CRF1 antagonist AS30 = CRF2 antagonist EPM Antagonist alone

  14. CP154,526 = CRF1 antagonist AS30 = CRF2 antagonist CPP

  15. Discussion • Intra-BNST administration of CRF axiogenic effects • Under basal levels of CRF neither antagonist effects anxiety • No caged controls

  16. CRF1 CRF2 Affects performance on EPM Affects performance in CPP

  17. CRF1 CRF2 Affects Unconditioned anxiety Affects Conditioned Aversive Learning

  18. 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) • Not remembering vs not acting on bad memories • CRF 1+ 2 both increase hippocampal LTP

  19. 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

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