The opposite role of hippocampal mGluR1 in fear conditioning in kindled and non-kindled rats

Brain Res. 2008 Jan 2:1187:184-93. doi: 10.1016/j.brainres.2007.10.010. Epub 2007 Oct 17.

Abstract

In the present paper, we analyzed the effects of hippocampal mGluR1 on the consolidation of a fear-conditioned response and on hippocampal glutamate and GABA concentration in rats subjected to the chemically-induced kindling of seizures. We hypothesized the important role of this glutamate receptor subpopulation in behavioural disturbances accompanying epilepsy. To this end, the behavioural and biochemical effects of selective mGluR1 and 5 receptor ligands were compared in sham and kindled animals (pentylenetetrazol-induced seizures). It was found that despite the fact that the freezing response to the aversively conditioned context was not changed by kindling itself, post-training intrahippocampal (dentate gyrus) injection of AIDA (a mGluR1 antagonist) oppositely influenced rat freezing behaviour in the non-kindled and kindled animals (i.e. the receptor ligand increased and decreased duration of the fear reaction, respectively). Kindling of seizures also enhanced the Glutamate/GABA ratio in the dorsal hippocampus (in vivo microdialysis), indicating an enhancement of excitatory processes in the brain. Altogether, the results showed that kindling of seizures led the potentiation of excitatory processes in the hippocampus, changing the role of the local mGluRs1 population in the conditioned fear learning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Chemistry / drug effects
  • Brain Chemistry / physiology
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology*
  • Convulsants
  • Epilepsy / chemically induced
  • Epilepsy / metabolism*
  • Epilepsy / physiopathology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Extracellular Fluid / metabolism
  • Fear / drug effects
  • Fear / physiology*
  • Glutamic Acid / analysis
  • Glutamic Acid / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Hippocampus / physiopathology
  • Kindling, Neurologic / drug effects
  • Kindling, Neurologic / metabolism*
  • Learning / physiology
  • Male
  • Microdialysis
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • gamma-Aminobutyric Acid / analysis
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Convulsants
  • Excitatory Amino Acid Antagonists
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1
  • Glutamic Acid
  • gamma-Aminobutyric Acid