The expression of contextual fear conditioning involves activation of a NMDA receptor-nitric oxide-cGMP pathway in the dorsal hippocampus of rats

Author(s)

Fabri, Denise R. S. ^[1] ; Hott, Sara C. ^{[1, 2]} ; Reis, Daniel G. ^{[1, 2]} ; Biojone, Caroline ^{[1, 2]} ; Correa, Fernando M. A. ^[1] ; Resstel, Leonardo B. M. ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: European Neuropsychopharmacology; v. 24, n. 10, p. 1676-1686, OCT 2014.
• Web of Science Citations: 12

Abstract

The dorsal portion of the hippocampus is a limbic structure that is involved in fear conditioning modulation in rats. Moreover, evidence shows that the local dorsal hippocampus glutamatergic system, nitric oxide (NO) and cGMP modulate behavioral responses during aversive situations. Therefore, the present study investigated the involvement of dorsal hippocampus NMDA receptors and the NO/cGMP pathway in contextual fear conditioning expression. Male Wistar rats were submitted to an aversive contextual conditioning session and 48 h later they were re-exposed to the aversive context in which freezing, cardiovascular responses (increase of both arterial pressure and heart rate) and decrease of tail temperature were recorded. The intra-dorsal hippocampus administration of the NMDA receptor antagonist AP7, prior to the re-exposure to the aversive context, attenuated fear-conditioned responses. The re-exposure to the context evoked an increase in NO concentration in the dorsal hippocampus of conditioned animals. Similar to AP7 administration, we observed a reduction of contextual fear conditioning after dorsal hippocampus administration of either the neuronal NO synthase inhibitor N-propyl-L-arginine, the NO scavenger c-PTIO or the guanylate cyclase inhibitor ODQ. Therefore, the present findings suggest the possible existence of a dorsal hippocampus NMDA/NO/cGMP pathway modulating the expression of contextual fear conditioning in rats. (C) 2014 Elsevier B.V. and ECNP. All rights reserved. (AU)

• FAPESP's process: 11/07332-3 - Possible role of dorsal hippocampus on behaviour and autonomic responses during defensive responses: involvement of NMDA receptor/nitric oxide and endocanabinoid
• Grantee: Leonardo Resstel Barbosa Moraes
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/09300-4 - Bed nucleus of the stria terminalis noradrenergic system modulates contextual fear conditionig: possible interaction with CRF and glutamatergic and nitrergic neurotransmission
• Grantee: Leonardo Resstel Barbosa Moraes
• Support Opportunities: Regular Research Grants