Nuclear magnetic resonance detection of increased cortical GABA in vigabatrin-treated rats in vivo.
1H Nuclear magnetic resonance ([1H]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.
Preece
N E
NE
Department of Biophysics, Hunterian Institute, London, England.
Jackson
G D
GD
Houseman
J A
JA
Duncan
J S
JS
Williams
S R
SR
D000614:Aminocaproates / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D001927:Brain Diseases / Q000139:chemically induced / Q000175:diagnosis; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000378:metabolism*
D000614:Aminocaproates; D000927:Anticonvulsants; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin