Benzodiazepine receptors in normal human brain, in Parkinson's disease and in progressive supranuclear palsy

Effects of etybenzatropine and diazepam on levodopa‐induced diphasic dyskinesias in Parkinson's disease

“…If such was the mechanism of benzodiazepines, parkinsonian signs would be expected to worsen after the administration of diazepam, since GABA agonists are assumed to activate the inhibitory striatonigral GABAergic system, thereby decreasing the activity of the nigrostriatal dopaminergic system (16). However, the fact that increased GABAergic transmission has been shown to potentiate apomorphine-induced turning in rats (17) and to improve levodopa-induced fluctuations in patients with Parkinson's disease (18) is in accordance with the beneficial action on levodopa-induced diphasic dyskinesias observed in this study on parkinsonism. To understand the mechanism of action of benzodiazepines in Parkinson's disease, one should also take into account the abundance of benzodiazepine receptors in human brain, particularly in the basal ganglia, and the lack of modification in their characteristics in the striatum of parkinsonian patients (19).…”

PET measures of benzodiazepine receptors in progressive supranuclear palsy

“…35 A single previous study of postmortem tissue in patients with PSP did not examine the cerebral cortex, but found GABA A receptors decreased only in the globus pallidus, a structure below the level of resolution in our study that we did not attempt to measure. 33 Taken together, there is little evidence that our findings can be explained by increased receptor occupancy. According to one study, the synthetic enzyme for GABA, glutamic acid decarboxylase (GAD), did not differ significantly from controls in the caudate nucleus or frontal cortex, but was reduced 49% in putamen, 59% in external pallidum, and 40% in hippocampus.…”

“…33 PET with FMZ failed to demonstrate any loss of benzodiazepine/GABA A receptors in AD, where there are clearly changes of intrinsic neurons in the cerebral cortex. The lower uptake of FMZ in this region raises the possibility that there might be a low signal to noise ratio obscuring smaller changes, but this is not borne out by the data.…”

Cholinergic vesicular transporters in progressive supranuclear palsy

“…1,2 Recent neuropathologic investigations also have noted involvement of cerebral cortical regions in PSP. 12 The caudate nucleus and putamen, however, are not sites of prominent neurofibrillary pathology in PSP, 13 and striatal benzodiazepine (BZ) binding sites are relatively preserved in vitro 10,14 and in vivo, 15 suggesting the possibility of altered regulation of D 2 receptors rather than degeneration of intrinsic D 2 -bearing striatal projection neurons. 12 The caudate nucleus and putamen, however, are not sites of prominent neurofibrillary pathology in PSP, 13 and striatal benzodiazepine (BZ) binding sites are relatively preserved in vitro 10,14 and in vivo, 15 suggesting the possibility of altered regulation of D 2 receptors rather than degeneration of intrinsic D 2 -bearing striatal projection neurons.…”