title: The expression of contextual fear conditioning involves activation of an NMDA receptor-nitric oxide pathway in the medial prefrontal cortex.
abstract: The ventral portion of medial prefrontal cortex (vMPFC) is involved in contextual fear-conditioning expression in rats. In the present study, we investigated the role of local N-methyl-D-aspartic acid (NMDA) glutamate receptors and nitric oxide (NO) in vMPFC on the behavioral (freezing) and cardiovascular (increase of arterial pressure and heart rate) responses of rats exposed to a context fear conditioning. The results showed that both freezing and cardiovascular responses to contextual fear conditioning were reduced by bilateral administration of NMDA receptor antagonist LY235959 (4 nmol/200 nL) into the vMPFC before reexposition to conditioned chamber. Bilateral inhibition of neuronal NO synthase (nNOS) by local vMPFC administration of the N omega-propyl-L-arginine (N-propyl, 0.04 nmol/200 nL) or the NO scavenger carboxy-PTIO (1 nmol/200 nL) caused similar results, inhibiting the fear responses. We also investigated the effects of inhibiting glutamate- and NO-mediated neurotransmission in the vMPFC at the time of aversive context exposure on reexposure to the same context. It was observed that the 1st exposure results in a significant attenuation of the fear responses on reexposure in vehicle-treated animals, which was not modified by the drugs. The present results suggest that a vMPFC NMDA-NO pathway may play an important role on expression of contextual fear conditioning.
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Av. Bandeirantes 3900, 14049-900, Ribeirão Preto, São Paulo, Brazil. leoresstel@yahoo.com.br
authors.forename: Leonardo Barbosa Moraes
authors.initials: LB
authors.lastname: Resstel
authors.forename: Fernando Morgan de Aguiar
authors.initials: FM
authors.lastname: Corrêa
authors.forename: Francisco Silveira
authors.initials: FS
authors.lastname: Guimarães
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005239:Fear / Q000502:physiology*; D046352:Freezing Reaction, Cataleptic / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D001565:Benzoates; D018691:Excitatory Amino Acid Antagonists; D007093:Imidazoles; D007546:Isoquinolines; C109599:N(omega)-propylarginine; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D009569:Nitric Oxide; D018698:Glutamic Acid; D001120:Arginine; C088643:LY 235959