Regional brain activation by bicuculline visualized by functional magnetic resonance imaging. Time-resolved assessment of bicuculline-induced changes in 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 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.
Reese
T
T
Core Technologies Area, Novartis Pharma Ltd, CH-4002 Basel, Switzerland.
Bjelke
B
B
Porszasz
R
R
Baumann
D
D
Bochelen
D
D
Sauter
A
A
Rudin
M
M
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D001810:Blood Volume; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D002560:Cerebrovascular Circulation; D003287:Contrast Media; D004195:Disease Models, Animal; D018756:GABA Antagonists / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009422:Nervous System Diseases / Q000175:diagnosis / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR
D003287:Contrast Media; D018756:GABA Antagonists; D001640:Bicuculline