Glutamatergic mechanisms of the dorsal periaqueductal gray matter modulate the expression of conditioned freezing and fear-potentiated startle. 2012

A E Reimer, and A R de Oliveira, and M L Brandão
Laboratório de Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil. aereimer@usp.br

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 (AP7) (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.

UI MeSH Term Description Entries
D008297 Male Males
D010487 Periaqueductal Gray Central gray matter surrounding the CEREBRAL AQUEDUCT in the MESENCEPHALON. Physiologically it is probably involved in RAGE reactions, the LORDOSIS REFLEX; FEEDING responses, bladder tonus, and pain. Mesencephalic Central Gray,Midbrain Central Gray,Central Gray Substance of Midbrain,Central Periaqueductal Gray,Griseum Centrale,Griseum Centrale Mesencephali,Periaqueductal Gray Matter,Substantia Grisea Centralis,Substantia Grisea Centralis Mesencephali,Central Gray, Mesencephalic,Central Gray, Midbrain,Gray Matter, Periaqueductal,Gray, Central Periaqueductal,Griseum Centrale Mesencephalus,Periaqueductal Grays, Central
D003214 Conditioning, Classical Learning that takes place when a conditioned stimulus is paired with an unconditioned stimulus. Reflex, Conditioned,Classical Conditioning,Classical Conditionings,Conditioned Reflex,Conditionings, Classical
D005239 Fear The affective response to an actual current external danger which subsides with the elimination of the threatening condition. Threat Cues,Threat Sensitivity,Cue, Threat,Fears,Sensitivity, Threat,Threat Cue,Threat Sensitivities
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013216 Reflex, Startle A complex involuntary response to an unexpected strong stimulus. The reaction involves physical movement away from the stimulus, MUSCLE CONTRACTION and limb flexion, BLINKING, and changes in HEART RATE, BLOOD PRESSURE, and RESPIRATION. Startle Reaction,Acoustic Startle Reflex,Reflex, Moro,Startle Response,Moro Reflex,Reaction, Startle,Reactions, Startle,Reflex, Acoustic Startle,Response, Startle,Responses, Startle,Startle Reactions,Startle Reflex,Startle Reflex, Acoustic,Startle Responses
D016194 Receptors, N-Methyl-D-Aspartate A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity. N-Methyl-D-Aspartate Receptor,N-Methyl-D-Aspartate Receptors,NMDA Receptor,NMDA Receptor-Ionophore Complex,NMDA Receptors,Receptors, NMDA,N-Methylaspartate Receptors,Receptors, N-Methylaspartate,N Methyl D Aspartate Receptor,N Methyl D Aspartate Receptors,N Methylaspartate Receptors,NMDA Receptor Ionophore Complex,Receptor, N-Methyl-D-Aspartate,Receptor, NMDA,Receptors, N Methyl D Aspartate,Receptors, N Methylaspartate
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D017470 Receptors, Glutamate Cell-surface proteins that bind glutamate and trigger changes which influence the behavior of cells. Glutamate receptors include ionotropic receptors (AMPA, kainate, and N-methyl-D-aspartate receptors), which directly control ion channels, and metabotropic receptors which act through second messenger systems. Glutamate receptors are the most common mediators of fast excitatory synaptic transmission in the central nervous system. They have also been implicated in the mechanisms of memory and of many diseases. Excitatory Amino Acid Receptors,Glutamate Receptors,Receptors, Excitatory Amino Acid,Excitatory Amino Acid Receptor,Glutamate Receptor,Receptor, Glutamate
D046352 Freezing Reaction, Cataleptic An induced response to threatening stimuli characterized by the cessation of body movements, except for those that are involved with BREATHING, and the maintenance of an immobile POSTURE. Cataleptic Immobilization Reaction,Immobilization Reaction, Cataleptic,Cataleptic Freezing Reaction,Cataleptic Freezing Reactions,Cataleptic Immobilization Reactions,Freezing Reactions, Cataleptic,Immobilization Reactions, Cataleptic,Reaction, Cataleptic Freezing,Reaction, Cataleptic Immobilization,Reactions, Cataleptic Freezing,Reactions, Cataleptic Immobilization

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