Differential localization of type I and type II benzodiazepine binding sites in substantia nigra

A number of studies have suggested the existence of multiple benzodiazepine binding sites in the brain^1-20. We have recently reported the physical separation of two apparent benzodiazepine binding site subtypes ²¹, the pharmacological properties, and distribution in tissue sections of which correspond to the putative type I and type II sites ^20,22. Benzodiazepine and γ-aminobutyric acid (GABA) receptors have been shown to interact²³, and lesions of the GABAergic striatonigral pathway, which lead to GABA supersensitivity^24,25, both increase the numbers of GABA binding sites^24,26 and enhance GABA-stimulated benzodiazepine binding²⁷. We demonstrate here that degeneration of striatonigral fibres increases the density of putative type I benzodiazepine binding sites in the substantia nigra and decreases the density of the putative type II sites. This suggests that type I sites that increase after denervation are postsynaptic, whereas the type II sites reduced by the lesion may be localized to axons or terminals of the striatonigral pathways.