Subthalamic ablation reverses changes in basal ganglia oxidative metabolism and motor response to apomorphine induced by nigrostriatal lesion in rats.
In Parkinson's disease, the functional architecture of the basal ganglia nuclei undergoes profound alterations, one of the most important of which is overactivity of the basal ganglia output nuclei. This phenomenon seems to be intimately related to pathological overactivity of the subthalamic nucleus, which directly modulates the basal ganglia output through its glutamatergic projections. In this study, we investigated the effects of unilateral subthalamic nucleus lesions on the activities of succinate dehydrogenase and cytochrome oxidase, two markers of neuronal activity, in rats with prior unilateral lesions of the nigrostriatal tract. We also explored the effect of subthalamic nucleus lesions on the rotational response to systemic apomorphine. Rats with unilateral lesions of the nigrostriatal tract showed ipsilateral increases in enzyme activity in the basal ganglia output nuclei, entopeduncular nucleus and substantia nigra pars reticulata. Selective subthalamic nucleus destruction completely reversed this phenomenon. In addition, subthalamic nucleus lesions abolished the rotational response to apomorphine. These results confirm that overactivity of the subthalamic nucleus plays a pivotal role in the functional alterations of basal ganglia associated with Parkinson's disease. They also shed further light on the neural mechanisms through which manipulations of subthalamic activity can ameliorate Parkinson's disease symptoms.
Blandini
F
F
Laboratory of Functional Neurochemistry, Neurological Institute C. Mondino, Pavia, Italy.
Garcia-Osuna
M
M
Greenamyre
J T
JT
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001479:Basal Ganglia / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D003576:Electron Transport Complex IV / Q000378:metabolism; D006651:Histocytochemistry; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior; D013378:Substantia Nigra / Q000502:physiology*; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013787:Thalamic Nuclei / Q000502:physiology*
D018491:Dopamine Agonists; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV; D001058:Apomorphine