Acute effects of gabapentin and pregabalin on rat forebrain cellular GABA, glutamate, and glutamine concentrations

Seizure. 2003 Jul;12(5):300-6. doi: 10.1016/s1059-1311(02)00295-9.

Abstract

The effects of antiepileptic drugs, gabapentin, pregabalin and vigabatrin, on brain gamma-aminobutyric acid (GABA), glutamate and glutamine concentrations were studied in Long Evans rats using proton magnetic resonance spectroscopy (MRS) of perchloric acid extracts. Cellular glutamate concentrations significantly decreased by 7% (P<0.05) 2 hours after intraperitoneal injection of 100mg/kg gabapentin and 4% (P<0.05) with 1000 mg/kg. No differences were observed in cellular GABA and cellular glutamine concentrations in rats treated with gabapentin. Pregabalin, an analogue of gabapentin, significantly decreased cellular glutamate concentrations by 4% (P<0.05), while no effect was observed on cellular GABA or glutamine concentrations in the healthy rat forebrain. Vigabatrin, used as a positive control to increase GABA levels, produced a 50% increase in cellular GABA compared to saline treated rats (P<0.003). Although, gabapentin and pregabalin are anticonvulsants designed to mimic GABA, these drugs do not raise cellular GABA levels acutely but modestly decreased cellular glutamate levels in our healthy rat forebrain model.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetates / pharmacology*
  • Amines*
  • Animals
  • Anticonvulsants / pharmacology*
  • Cyclohexanecarboxylic Acids*
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Gabapentin
  • Glutamic Acid / analysis*
  • Glutamine / analysis*
  • Injections, Intraperitoneal
  • Magnetic Resonance Spectroscopy
  • Male
  • Neurons / chemistry
  • Neurons / drug effects
  • Pregabalin
  • Prosencephalon / chemistry
  • Prosencephalon / drug effects*
  • Rats
  • Rats, Long-Evans
  • Vigabatrin / pharmacology
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / analysis*
  • gamma-Aminobutyric Acid / pharmacology*

Substances

  • Acetates
  • Amines
  • Anticonvulsants
  • Cyclohexanecarboxylic Acids
  • Excitatory Amino Acid Antagonists
  • Glutamine
  • Glutamic Acid
  • Pregabalin
  • gamma-Aminobutyric Acid
  • Gabapentin
  • Vigabatrin