Bed nucleus of the stria terminalis noradrenergic system modulates contextual conditioned emotional response: involvement of CRF1 receptors and NMDA-NO pathaway

Author(s)

Sara Cristina Hott

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2015-03-27

Examining board members

Leonardo Resstel Barbosa Moraes; Norberto Garcia Cairasco; Antonio de Pádua Carobrez; Vanessa Beijamini Harres; Helio Zangrossi Junior

• Advisor: Leonardo Resstel Barbosa Moraes

Abstract

The bed nucleus of the stria terminalis (BNST) is a limbic structure that has been associated to the expression of anxiety responses. BNST is one of the main targets of noradrenergic innervation in the central nervous system and evidence suggests an activation of this neurotransmission in aversive situations, particularly fear conditioning. Thus, the present study investigated the involvement of BNST noradrenergic system in modulating of behavioral and autonomic responses induced by contextual fear conditioning (CFC) in rats. The conditioned animals showed significant behavioral response (freezing) and autonomic changes such as increased in mean arterial pressure, heart rate and decreased in the tail temperature after re-exposure to context. These effects were attenuated by intra-BNST injection of L-propranolol and phentolamine, non-selective antagonists of and -adrenoceptors, respectively. Additionally, it was also observed that the administration of WB4101, a selective 1 adrenoceptor antagonist, and CGP20712, selective 1 adrenoceptor antagonist, in the BNST reduced conditioned emotional response (CER), suggesting that the BNST noradrenergic neurotransmission through the activation of adrenergic receptors, especially 1 and 1-adrenergic receptors, is involved in the expression of CER. Moreover, evidence shows that activation of 1 adrenoreceptor increases the release of glutamate by CRF1 receptor activation. Therefore, this study also investigated the involvement of CRF, glutamatergic and nitrergic systems in the noradrenergic neurotransmission modulation of CER induced by CFC. Administration of reboxetine, a norepinephrine reuptake inhibitor, significantly increased freezing behavior and induced autonomic responses after re-exposure to aversive context. These effects were blocked by previous administration of the antagonist of 1 and 1-adrenoceptor, WB4101 and CGP20712 respectively, CRF1 antagonist, CP376395, an NMDA receptor antagonist, AP7, and inhibitor of neuronal nitric oxide synthase, NPLA. Similar to reboxetine, urocortin significantly induced CER. These effects induced by urocortin were blocked by CP376395, NPLA and AP7, but not by CGP20712 and WB4101. The present study demonstrates that BNST noradrenergic system is involved in CER observed in CFC model, possibly interacting with CRF, nitrergic and glutamatergic systems. (AU)

• FAPESP's process: 11/13299-9 - Bed nucleus of the stria terminalis noradrenergic system modulates contextual fear conditionig: possible interaction with CRF and glutamatergic neurotransmission
• Grantee: Sara Cristina Hott
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)