Differences in alpha7 nicotinic acetylcholine receptor binding in motor symptomatic and asymptomatic MPTP-treated monkeys.

We studied [(125)I]alpha-bungarotoxin (btx) binding to alpha7 nicotinic acetylcholine receptors in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposed macaque monkeys. [(125)I]alpha-Btx binds throughout the normal monkey brain, with the greatest density in the thalamic nuclei and with moderate to low binding in the hippocampus, prefrontal cortex, caudate, putamen, and substantia nigra. Chronic administration of low doses of MPTP resulted in animals with stable cognitive deficits without overt parkinsonian motor symptoms. [(125)I]alpha-Btx binding in the brains of these animals was significantly increased in the outermost layers of the supplementary motor cortex (area 6M, approximately 50%), primary motor cortex (area 4, approximately 112%) and throughout the putamen (approximately 50-72%). In contrast, there was no change in [(125)I]alpha-btx binding in the brain regions thought to be involved in mediating the cognitive functions impaired in these monkeys (e.g., the hippocampus, areas 9/46D and 46D of the principal sulcus, and area 24c of the cingulate sulcus). Animals with cognitive dysfunction that received escalating doses of MPTP for >6 months developed motor signs of parkinsonism which were indistinguishable from those seen in animals rendered acutely parkinsonian with short term administration of large doses of MPTP. These two "motor symptomatic" groups had significantly increased [(125)I]alpha-btx binding only in the dorsolateral putamen. Immunohistochemical studies showed that the increased [(125)I]alpha-btx binding, when observed, was associated with enhanced immunohistochemical staining localized to neurons and was not a result of an astrocytic response to MPTP. These results suggest that the increase in alpha7 nicotinic acetylcholine receptor expression in the chronic low-dose MPTP treated, motor asymptomatic monkeys may be a part of compensatory processes contributing to the maintained motor functioning in these animals.