title: The expression of contextual fear conditioning involves activation of a NMDA receptor-nitric oxide-cGMP pathway in the dorsal hippocampus of rats.
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.
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Denise R S
authors.initials: DR
authors.lastname: Fabri
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil.
authors.forename: Sara C
authors.initials: SC
authors.lastname: Hott
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Reis
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil.
authors.forename: Caroline
authors.initials: C
authors.lastname: Biojone
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Fernando M A
authors.initials: FM
authors.lastname: Corrêa
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil. Electronic address: leoresstel@yahoo.com.br.
authors.forename: Leonardo B M
authors.initials: LB
authors.lastname: Resstel
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects / Q000502:physiology; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism*; D004597:Electroshock; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013623:Tail
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D006152:Cyclic GMP
keywords: Autonomic responses; Conditioned emotional response; Glutamatergic system; Hippocampus; Nitric oxide