The reduction in paired-pulse inhibition in the rat hippocampus by gabapentin is independent of GABA(B) receptor receptor activation

Epilepsy Res. 1999 Feb;33(2-3):169-76. doi: 10.1016/s0920-1211(98)00083-7.


Previously we have shown that gabapentin causes a reduction of paired-pulse inhibition in the dentate gyrus of the urethane-anesthetized rat, which looks very much like the effect of baclofen on paired-pulse inhibition. In addition, it has been proposed that gabapentin increases release of GABA from non-vesicular stores and may, therefore, interact with GABA(B) mechanisms. Here we tested the ability of a GABA(B) agonist, baclofen, and a GABA(B) antagonist, CGP35348, to block the effect of gabapentin on paired-pulse inhibition in the dentate gyrus in urethane-anesthetized adult Sprague-Dawley rats. Both baclofen (6 mg/kg) and gabapentin (100 mg/kg) caused a long-lasting reduction of paired-pulse inhibition in the dentate gyrus when given alone or in combination. CGP35348 (45 mg/kg) blocked the effect of baclofen on paired-pulse inhibition, but did not alter the effect of gabapentin. Gabapentin also caused a reduction of inhibition in the CA1 region, indicating that its effect is not specific for the dentate gyrus. These results suggest that gabapentin produces its effect on paired-pulse inhibition independent from the effect of baclofen and not through non-vesicular release of GABA interacting with the GABA(B) receptor system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetates / pharmacology*
  • Amines*
  • Animals
  • Anticonvulsants / pharmacology*
  • Baclofen / antagonists & inhibitors
  • Baclofen / pharmacology
  • Cyclohexanecarboxylic Acids*
  • Dentate Gyrus / drug effects*
  • Dentate Gyrus / physiology
  • Electric Stimulation / methods
  • GABA Agonists / pharmacology
  • GABA Antagonists / pharmacology
  • Gabapentin
  • Male
  • Neural Inhibition / drug effects*
  • Organophosphorus Compounds / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-B / physiology*
  • gamma-Aminobutyric Acid*


  • Acetates
  • Amines
  • Anticonvulsants
  • Cyclohexanecarboxylic Acids
  • GABA Agonists
  • GABA Antagonists
  • Organophosphorus Compounds
  • Receptors, GABA-B
  • gamma-Aminobutyric Acid
  • Gabapentin
  • CGP 35348
  • Baclofen