Elevated endogenous GABA level correlates with decreased fMRI signals in the rat brain during acute inhibition of GABA transaminase.
Vigabatrin and gabaculine, both highly specific inhibitors of GABA (gamma-aminobutyric acid) transaminase, cause significant elevation of endogenous GABA levels in brain. The time course of GABA concentration after acute GABA transaminase inhibition was measured quantitatively in the alpha-chloralose-anesthetized rat brain using in vivo selective homonuclear polarization transfer spectroscopy. The blood oxygenation level-dependent (BOLD) effect in functional magnetic resonance imaging (fMRI) has been considered to be coupled tightly to neuronal activation via the metabolic demand of associated glutamate transport. Correlated with the rise in endogenous GABA level after vigabatrin or gabaculine treatment, the intensity of BOLD-weighted fMRI signals in rat somatosensory cortex during forepaw stimulation was found to be reduced significantly. These results are consistent with previous findings that inhibition of GABA transaminase leads to augmented GABA release and potentiation of GABAergic inhibition.
Chen
Zhengguang
Z
Molecular Imaging Branch, NIMH, Bethesda, MD 20892-1527, USA.
Silva
Afonso C
AC
Yang
Jehoon
J
Shen
Jun
J
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000201:enzymology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013003:Somatosensory Cortex / Q000187:drug effects / Q000201:enzymology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014110:Touch / Q000187:drug effects / Q000502:physiology; D020888:Vigabatrin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D003509:Cyclohexanecarboxylic Acids; D004791:Enzyme Inhibitors; C012987:gabaculine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin