Functional and neuroreceptor imaging of the brain in bicuculline-induced dystonic rats.
Dystonia is an involuntary movement disorder dominated by sustained muscle contractions that frequently cause twisting, repetitive movements, and postural changes. The purpose of this study was to determine the mechanism causing dystonia. We therefore employed a rat model of dystonia, which was induced by injecting (-)-bicuculine methiodide (BM), a gamma-aminobutyric acid A (GABA(A)) receptor antagonist, stereotaxically into the ventrolateral thalamic nuclei. Cerebral glucose metabolism reflecting cerebral activities and densities of central benzodiazepine and adenosine A(1) receptors that play an inhibitory role in neural excitation were evaluated in the brain by ex vivo autoradiography using appropriate (14)C/(18)F- or (11)C-labeled tracers. The dystonic signs were accompanied by increased glucose metabolism in the thalamus, substantia nigra, globus pallidus, and striatum. However, central benzodiazepine receptor density was not altered, and adenosine A(1) receptor density was reduced in the hippocampus. These results indicate the activation of a basal ganglia-thalamo-cortical motor circuit, which consists of the thalamus, substantia nigra, globus pallidus, and striatum. In this context, the activation of the above circuit has been reported in human dystonia patients. The decreased adenosine A(1) receptor density in the hippocampus might be related to a transient hippocampal dysfunction due to an acute type of dystonia. In conclusion, we have succeeded in generating a rat model of dystonia, and observed the activation of the basal ganglia-thalamo-cortical motor circuit that is related to dystonia.
Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo, Japan.
QingGeLeTu
Yukihisa
Y
Suzuki
Motohiro
M
Kiyosawa
Kiichi
K
Ishiwata
Manabu
M
Mochizuki
D000818:Animals; D001345:Autoradiography; D001640:Bicuculline / Q000633:toxicity; D001921:Brain / Q000000981:diagnostic imaging*; D004195:Disease Models, Animal; D004421:Dystonia / Q000139:chemically induced / Q000000981:diagnostic imaging*; D004525:Efferent Pathways / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D008297:Male; D011868:Radioisotopes; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000378:metabolism
D011868:Radioisotopes; D043682:Receptor, Adenosine A1; D005947:Glucose; D001640:Bicuculline