Central muscarinic receptor degeneration following 6-hydroxydopamine lesion in mice

Adult mice received two 70 μg doses of 6-hydroxydopamine intracisternally 72 hours apart, and the muscarinic binding properties of discrete brain regions were then investigated at various time intervals. Three days after the second injection, ³H-norepinephrine uptake was drastically reduced in all brain regions studied, and a distinct decrease in muscarinic receptor density was observed in the striatum (-18%), medulla-pons (-17%) and cerebellum (-15%) of lesioned animals as compared with controls. No changes were detected in muscarinic receptor density in the cortex or the hippocampus of treated animals, nor were any changes seen in the affinity of the labelled ligand for its receptor or in the displacement properties of the muscarinic binding by agonists in any of the regions studied. These effects still persisted after 60 days, with a further reduction in striatal muscarinic density to 74% of control values. Data are interpreted with respect to the proposed model for cholinergic modulation of central catecholamine release and cholinergic-catecholaminergic interactions in the striatum.