Changes in extracellular levels of amygdala amino acids in genetically fast and slow kindling rat strains

Brain Res. 2002 Aug 9;946(1):31-42. doi: 10.1016/s0006-8993(02)02821-4.

Abstract

A neurochemical basis for many of the epilepsies has long been suspected to result from an imbalance between excitatory and inhibitory neurotransmitter mechanisms. Data supporting changes in extrasynaptic amino acid levels during epileptogenesis, however, remain controversial. In the present study, we used in vivo microdialysis to measure the levels of extracellular GABA (gamma-aminobutyric acid) and glutamate during seizure development in rats with a genetic predisposition for (Fast), or against (Slow), amygdala kindling. Dialysates were collected from both amygdalae before, during, and up to 12 min after a threshold-triggered amygdala afterdischarge (AD). One hour later, samples were again collected from both amygdalae in response to a hippocampal threshold AD. Daily amygdala kindling commenced the next day but without dialysis. After the rats were fully kindled, the same protocol was again employed. Amino acid levels were not consistently increased above baseline with triggered seizures in either strain. Instead, before kindling, a focal seizure in the Slow rats was associated with a large decrease in GABA in the non-stimulated amygdala, while amino acid levels in the Fast rats remained near baseline in both amygdalae. Similar results were seen after kindling. By contrast, before and after kindling, hippocampal stimulation caused large decreases in all amino acid levels in both amygdalae in both strains. These data suggest that, in response to direct stimulation, extracellular amino acid concentrations remain stable in tissues associated with either greater natural (Fast) or induced (kindled Fast/Slow) excitability, but are lowered with indirect stimulation (hippocampus) and/or low excitability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism*
  • Amygdala / metabolism*
  • Animals
  • Differential Threshold
  • Electrophysiology
  • Extracellular Space / metabolism*
  • Genetic Predisposition to Disease
  • Glutamic Acid / metabolism
  • Hippocampus / physiology
  • Kindling, Neurologic / genetics
  • Kindling, Neurologic / physiology*
  • Male
  • Rats
  • Rats, Inbred Strains / genetics
  • Seizures / etiology
  • Seizures / physiopathology
  • Time Factors
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Amino Acids
  • Glutamic Acid
  • gamma-Aminobutyric Acid