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

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.