Antiparkinsonian and Behavioral Effects of Inactivation of the Substantia Nigra Pars Reticulata in Hemiparkinsonian Primates

• Published in: Experimental neurology Vol. 167; no. 2; pp. 410 - 424
• Main Authors: Wichmann, Thomas, Kliem, Michele A., DeLong, Mahlon R.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.02.2001; Elsevier
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Behavior, Animal - drug effects; Biological and medical sciences; Carrier Proteins - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dopamine Plasma Membrane Transport Proteins; Excitatory Amino Acid Agonists - administration & dosage; GABA Agonists - administration & dosage; globus pallidus; ibotenic acid; Ibotenic Acid - administration & dosage; lesion; Macaca mulatta; Medical sciences; Membrane Glycoproteins; Membrane Transport Proteins; Microinjections; Motor Activity - drug effects; MPTP; muscimol; Muscimol - administration & dosage; Nerve Tissue Proteins; Neurology; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Parkinson Disease, Secondary - chemically induced; Parkinson Disease, Secondary - drug therapy; Parkinson Disease, Secondary - physiopathology; Parkinson's disease; primate; Substantia Nigra - drug effects; Substantia Nigra - pathology; Substantia Nigra - physiopathology; substantia nigra pars reticulata; subthalamic nucleus; primate; Parkinson's disease; substantia nigra pars reticulata; muscimol; ibotenic acid; subthalamic nucleus; MPTP; globus pallidus; lesion; Nervous system diseases; Agonist; Akinesia; Motor system disorder; Pathogenesis; Gabaergic agonist; Monkey; Parkinson disease; Basal ganglion; Inactivation; Cerebral disorder; Saccadic eye movement; Parkinsonism; Gabaergic receptor; Vertebrata; Generation; Mammalia; Animal; Central nervous system disease; Primates; Degenerative disease; Neurological disorder; Extrapyramidal syndrome
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1006/exnr.2000.7572

Altered activity in one of the output nuclei of the basal ganglia, the internal segment of the globus pallidus, is known to play an important role in the generation of parkinsonism. These inactivation studies tested the hypothesis that altered activity in the second major output nucleus of the basal ganglia, the substantia nigra pars reticulata (SNr), also contributes to parkinsonian motor signs. To this end, three rhesus monkeys were rendered hemiparkinsonian by intracarotid injections of MPTP. The animals then received intra-SNr injections of the GABAA receptor agonist muscimol to inactivate small portions of the SNr. Before and after these injections, parkinsonian motor signs were evaluated with a battery of behavioral observation methods. Injections into the centrolateral SNr reduced contralateral limb akinesia and bradykinesia in two animals. By contrast, medial injections induced generalized activation, contralateral turning, and saccadic eye movements in all animals. Injections in the most lateral and posterior portions of the nucleus had no effects. Two of the animals also received ibotenic acid lesions of the SNr, followed by a series of similar observations. These injections induced improvements in limb akinesia, postural improvements, and turning. The experiments suggest that the anterolateral “motor” territory of the SNr is involved in the development of appendicular parkinsonian motor signs.