[³]PIRENZEPINE BINDING IN RAT CORPUS STRIATUM DECREASES AFTER HEMITRANSECTION OF THE NIGRO‐STRIATAL PATHWAY

Abstract

The localization and pharmacologic characterization of muscarinic receptors possibly regulating the release of dopamine (DA) in rat corpus striatum were investigated by in vitro binding with [3H]pirenzepine ([3H]PZ) after hemitransection of the nigro-striatal pathway. DA levels in the corpus striatum ipsilateral to the lesion were substantially reduced by 66% compared with the unlesioned side after 8 days. The uptake of [3H]DA was also diminished by 63%. A significant decrease in the specific binding of [3H]PZ of 42% was seen in the corpus striatum ipsilateral to the lesion. The data indicate a loss of binding sites, whereas the lesion caused no change in the affinity constant for the muscarinic antagonist. The results support those previously obtained in studies of the muscarinic modulation of [3H]DA release from striatal synaptosomes and favor the idea that at least part of the muscarinic receptors regulating striatal DA release are localized on the nigro-striatal axon terminals and belong to the pirenzepine-sensitive subtype.

Altered Muscarinic and Nicotinic Receptor Densities in Cortical and Subcortical Brain Regions in Parkinson's Disease

“…As dopaminergic neurones projecting from the siibstantia nigra to the striatum degenerate in Parkinson's disease (Jellinger, 1987), the decrease in the number of [3H]pirenzepine binding sites in the striatuni could be explained by a possible location of M, receptors on nigrostriatal dopaminergic axon terminals. This view is underlined by the finding that after heniitransection of the nigrostriatal pathway in the rat, a substantial reduction of [3H]pirenzepine receptors is observed in the striatum ipsilateral to the lesion (Pittaluga et al, 1987).…”