NMDA and AMPA/kainate glutamatergic receptors in the prelimbic medial prefrontal cortex modulate the elaborated defensive behavior and innate fear-induced antinociception elicited by GABAA receptor blockade in the medial hypothalamus.
The aim of the present study was to investigate the involvement of N-methyl-d-aspartate (NMDA) and amino-3-hydroxy-5-methyl-isoxazole-4-proprionate (AMPA)/kainate receptors of the prelimbic (PL) division of the medial prefrontal cortex (MPFC) on the panic attack-like reactions evoked by γ-aminobutyric acid-A receptor blockade in the medial hypothalamus (MH). Rats were pretreated with NaCl 0.9%, LY235959 (NMDA receptor antagonist), and NBQX (AMPA/kainate receptor antagonist) in the PL at 3 different concentrations. Ten minutes later, the MH was treated with bicuculline, and the defensive responses were recorded for 10 min. The antagonism of NMDA receptors in the PL decreased the frequency and duration of all defensive behaviors evoked by the stimulation of the MH and reduced the innate fear-induced antinociception. However, the pretreatment of the PL cortex with NBQX was able to decrease only part of defensive responses and innate fear-induced antinociception. The present findings suggest that the NMDA-glutamatergic system of the PL is critically involved in panic-like responses and innate fear-induced antinociception and those AMPA/kainate receptors are also recruited during the elaboration of fear-induced antinociception and in panic attack-related response. The activation of the glutamatergic neurotransmission of PL division of the MPFC during the elaboration of oriented behavioral reactions elicited by the chemical stimulation of the MH recruits mainly NMDA receptors in comparison with AMPA/kainate receptors.
Departamento de Farmacologia, Laboratório de Neuroanatomia & Neuropsicobiologia.
Renato Leonardo
RL
de Freitas
Carlos José
CJ
Salgado-Rohner
Audrey Francisco
AF
Biagioni
Priscila
P
Medeiros
Jaime Eduardo Cecílio
JE
Hallak
José Alexandre S
JA
Crippa
Norberto Cysne
NC
Coimbra
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001640:Bicuculline / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D007033:Hypothalamus, Middle / Q000187:drug effects / Q000502:physiology*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D059226:Nociceptive Pain / Q000188:drug therapy / Q000503:physiopathology; D058748:Pain Perception / Q000187:drug effects / Q000502:physiology*; D010200:Panic / Q000187:drug effects / Q000502:physiology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D007546:Isoquinolines; D011810:Quinoxalines; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C088643:LY 235959; D001640:Bicuculline
N-methyl-d-aspartate receptors; amino-3-hydroxy-5-methyl-isoxazole-4-proprionate/kainate receptors; dorsomedial hypothalamus; innate fear-induced antinociception; panic-like behavior, prelimbic medial prefrontal cortex; γ-aminobutyric acid-A receptors