Reduction in benzodiazepine receptors associated with Purkinje cell degeneration in 'nervous' mutant mice [22]

Phil Skolnick, Peter J. Syapin, Beth A. Paugh, Steven M. Paul

Research output: Contribution to journalLetterpeer-review

49 Scopus citations


HIGH affinity benzodiazepine binding sites which are both stereospecific and saturable1-3 have recently been characterised in the mammalian central nervous system (CNS). The good correlations obtained between the binding affinities of a series of benzodiazepines and their potencies as anticonvulsants, anxiolytics and muscle relaxants strongly suggest that these sites may function as pharmacological receptors for the benzodiazepines 1,4. Although both the gross anatomical3,5 and subcellular distribution6 of these sites have been described, the cellular localisation of these sites is not known, nor has a direct functional link been established between benzodiazepine binding sites and the neuropharmacological effects of these drugs. We now report that 'nervous' mutant mice, which undergo a selective loss of more than 90% of their cerebellar Purkinje cells during maturation7,8, have a marked reduction in the number of cerebellar benzodiazepine receptors. This loss in benzodiazepine receptors seems to be confined to the cerebellum, and is not accompanied by an alteration in the affinity of the receptor for diazepam. These data clearly demonstrate the loss of benzodiazepine receptors in a cell type which has been shown to be both neurochemically9 and electrophysiologically10 sensitive to benzodiazepines, thus providing evidence that benzodiazepine receptors function in the pharmacological actions of these drugs.

Original languageEnglish
Pages (from-to)397-399
Number of pages3
Issue number5695
StatePublished - 1979


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