NUCLEAR-MAGNETIC-RESONANCE DETECTION OF INCREASED CORTICAL GABA IN VIGABATRIN-TREATED RATS IN-VIVO

H-1 Nuclear magnetic resonance ([H-1]NMR) spectroscopy was used to detect elevation of gamma-aminobutyric acid (GABA) in rat brain after administration of the antiepileptic drug vigabatrin (VGB). Rats were treated for 3 weeks with VGB added to their drinking water to deliver a dose of 250 mg/kg body weight per day. NMR spectroscopy was performed noninvasively in vivo, and a GABA concentration of 6.0 +/- 2.3 mmol/kg wet weight (mean +/- SD, n = 5) was measured. GABA could not be detected in control animals in vivo. Postmortem GABA levels of 1.3 +/- 0.5 and 4.5 +/- 1.0 mmol/kg (mean +/- SD, n = 5) were measured in perchloric acid extracts of frozen brain from control and treated animals, respectively. Noninvasive measurement of increased cerebral GABA should allow detailed studies of the pharmacology of GABA-increasing drugs in vivo. With future developments, these measurements may be feasible in human subjects.