Antiparkinsonian and behavioral effects of inactivation of the substantia nigra pars reticulata in hemiparkinsonian primates

Altered activity in one of the output nuclei of the basal ganglia, the inte rnal segment of the globus pallidus, is known to play an important role in the generation of parkinsonism, These inactivation studies tested the hypot hesis that altered activity in the second major output nucleus of the basal ganglia, the substantia nigra pars reticulata (SNr), also contributes to p arkinsonian motor signs. To this end, three rhesus monkeys were rendered he miparkinsonian by intracarotid injections of MPTP. The animals then receive d intra-SNr injections of the GABA, 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 method s. Injections into the centrolateral SNr reduced contralateral limb akinesi a and bradykinesia in two animals. By contrast, medial injections induced g eneralized 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 lesi ons of the SNr, followed by a series of similar observations. These injecti ons induced improvements in limb akinesia, postural improvements, and turni ng. The experiments suggest that the anterolateral "motor" territory of the SNr is involved in the development of appendicular parkinsonian motor sign s. (C) 2001 Academic Press.