4.5 Article

GLUTAMATERGIC MECHANISMS OF THE DORSAL PERIAQUEDUCTAL GRAY MATTER MODULATE THE EXPRESSION OF CONDITIONED FREEZING AND FEAR-POTENTIATED STARTLE

Journal

NEUROSCIENCE
Volume 219, Issue -, Pages 72-81

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2012.06.005

Keywords

fear conditioning; dorsal periaqueductal gray matter; AMPA/Kainate receptor; NMDA receptor; fear-potentiated startle; conditioned freezing

Categories

Funding

  1. FAPESP [11/00041-3, 10/50669-6]
  2. CNPq [472029/2006-0, 143018/2008-6]
  3. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [11/00041-3] Funding Source: FAPESP

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It is well known that excitatory amino acids induce unconditioned fear responses when locally injected into the dorsal periaqueductal gray matter (dPAG). However, there are only few studies about the involvement of excitatory amino acids mediation in dPAG in the expression of conditioned fear. The present series of experiments evaluates the participation of AMPA/Kainate and NMDA glutamatergic receptors of dPAG in the expression of conditioned fear, assessed by the fear-potentiated startle (FPS) and conditioned freezing responses. Wistar rats were subjected to fear conditioning to light. Twenty-four hours later, they received intra-dPAG injections of kainic acid or NMDA (AMPA/Kainate and NMDA agonists) and 1,2,3,4-Tetrahydro-6-nitro-2, 3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium salt hydrate (NBQX) or D(-)-2-Amino-7-phosphonoheptanoic acid (APT) (AMPA/Kainate and NMDA antagonists) and were submitted to the FPS test. Conditioned freezing response was simultaneously measured. Effects of drug treatment on motor activity were evaluated in the open-field test. Intra-dPAG injections of glutamatergic agonists enhanced conditioned freezing and promoted pro-aversive effects in the FPS. Lower doses of the agonists had no effect or enhanced FPS whereas higher doses disrupted FPS, indicating a non-monotonic relationship between fear and FPS. The antagonist NBQX had no significant effects while AP7 decreased conditioned freezing but did not affect FPS. Both antagonists reduced the effects of the agonists. The obtained results cannot be attributed to motor deficits. The results suggest an important role of the AMPA/Kainate and NMDA mechanisms of the dPAG in the expression of conditioned freezing and FPS. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

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