Tohoku J. Exp. Med., 2009, 217(4)

Functional and Neuroreceptor Imaging of the Brain in Bicuculline-Induced Dystonic Rats

QINGGELETU,^1,2 YUKIHISA SUZUKI,^1,2 MOTOHIRO KIYOSAWA,^1,2 KIICHI ISHIWATA² and MANABU MOCHIZUKI¹

¹Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo, Japan
²Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

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 A₁ receptors that play an inhibitory role in neural excitation were evaluated in the brain by ex vivo autoradiography using appropriate ¹⁴C/¹⁸F- or ¹¹C-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 A₁ 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 A₁ 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.

keywords —— adenosine A₁ receptor; bicuculline methiodide; central benzodiazepine receptor density; cerebral glucose metabolism; dystonia.

© 2009 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2009, 217, 313-320

Correspondence: Motohiro Kiyosawa, M.D., Ph.D., Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakaecho, Itabashi, Tokyo, Japan.

e-mail: m.kiyosawa.oph@tmd.ac.jp