Loss of cannabinoid receptors in the substantia nigra in huntington's disease

Abstract

Previous antoradiographic studies in rate using [ 3CP55,940 have demonstrated the cannabinoid receptor to be located on the axon terminals of striatal efferent neurons projecting to the globus pallidus and substantia nigra. 9Because these neurons are selectively tost in Hantington's disease, 8 a loss of [ 3H]CP55,940 binding is predicted in the sabstantia nigra of the Huntington's disease brain. We have used autoradiography to compare the binding of [ 3H]CP55,940 in the substantia nigra of Huntington's disease and neurologically normal brrains. The results have demonstrated that cannabinoid receptors in the normal human sabstantia nigra are discreetly localized within the substantia nigra pars reticulata. In cntrast, the Huntington's disease brains show a massive loss (97.5%) of cannabinoid receptor binding in the substantia nigra pars reticulata. These results show that ta the substantia nigra of the bumman brain cannabinoid receptors are located on striatonigral terminals which degenerate in Huntington's disease.