Functional magnetic resonance imaging (fMRI) has been applied to study rat focal brain activation induced by intravenous administration of the GABA(A) antagonist bicuculline. Using magnetite nanoparticles as a blood pool contrast agent, local changes in cerebral blood volume (CBV) were assessed with high temporal (10 s) and spatial (0.35 x 0.6 mm(2)) resolutions. Upon infusion of the bicuculline region-specific increases in CBV have been observed, suggesting CBV to reflect brain activity. During the first 2 min, the signal increases were predominant in the cortex, followed by increases in other brain areas, such as the caudate putamen, thalamus and cerebellum. Ten minutes after the start of infusion, a dominant response was observed in the thalamus, 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 GABA(A) binding sites. This study suggests that pharmacological fMRI, displaying brain function at the highly specific level of drug-receptor interaction, should foster our understanding of normal and pathological brain function.
Copyright 2000 John Wiley & Sons, Ltd.