Regional brain activation by bicuculline visualized by functional magneticresonance imaging. Time-resolved assessment of bicuculline-induced changesin local cerebral blood volume using an intravascular contrast agent

Functional magnetic resonance imaging (fMRI) has been applied to study rat focal brain activation induced by intravenous administration of the GABAA a ntagonist bicuculline. Using magnetite nanoparticles as a blood pool contra st agent, local changes in cerebral blood volume (CBV) were assessed with h igh temporal (10 s) and spatial (0.35 x 0.6 mm(2)) resolutions. Upon infusi on of the bicuculline region-specific increases in CBV have been observed, suggesting CBV to reflect brain activity. During the first 2 min, the signa l increases were predominant in the cortex, followed by increases in other brain areas, such as the caudate putamen, thalamus and cerebellum. Ten minu tes after the start of infusion, a dominant response was observed in the th alamus, while in the caudate putamen a biphasic response pattern was seen. The magnitude of the signal responses in all brain regions was dependent on the dose of bicuculline and, in general, matched the known distribution of GABAA binding sites. This study suggests that pharmacological fMRI, displa ying brain function at the highly specific level of drug-receptor interacti on, should foster our understanding of normal and pathological brain functi on. Copyright (C) 2000 John Wiley & Sons, Ltd.