title: Acute effects of gabapentin and pregabalin on rat forebrain cellular GABA, glutamate, and glutamine concentrations.
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.
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT 06520-8018, USA.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Errante
authors.forename: Ognen A C
authors.initials: OA
authors.lastname: Petroff
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000588:Amines; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003509:Cyclohexanecarboxylic Acids; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D000077206:Gabapentin; D018698:Glutamic Acid / Q000032:analysis*; D005973:Glutamine / Q000032:analysis*; D007274:Injections, Intraperitoneal; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000187:drug effects; D000069583:Pregabalin; D016548:Prosencephalon / Q000737:chemistry / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D020888:Vigabatrin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000032:analysis* / Q000494:pharmacology*
chemical_list: D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D005973:Glutamine; D018698:Glutamic Acid; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D020888:Vigabatrin