Benzodiazepine and muscarinic receptors in the neocortex were studied using homogenate binding techniques and in vitro autoradiography (ARG). Tritiated flunitrazepam was used to bind to the benzodiazepine portion of the gamma-aminobutyric acid receptor. Tritiated quinuclidnyl benzilate was used to locate the muscarinic receptor. Tissue samples from four areas of neocortex from cases of Parkinson's disease, Alzheimer's disease and age-matched controls were used for homogenate binding experiments to estimate binding parameters. Tissue for ARG provided more detailed anatomical localization of the relevant receptors. Homogenate binding studies showed that the receptor density, as measured by maximum binding capacity for tritiated flunitrazepam, was significantly reduced in the frontal cortex in Parkinson's disease. In Alzheimer's disease there was reduced binding of flunitrazepam in all portions of the neocortex studied, reaching statistical significance in the frontal and temporal cortex. The dissociation constant, indicating receptor affinity for flunitrazepam, was unaltered in all areas studied. ARG demonstrated that the distribution of benzodiazepine receptor loss within different cortical layers was distinct in Parkinson's and Alzheimer's disease. In control brains, the greatest density of benzodiazepine receptors was seen in regions corresponding to layers II and III. This peak was greatly reduced in the frontal cortex of Parkinson's disease, while in Alzheimer's disease the loss was more uniform. There was no significant alteration in the binding parameters of the muscarinic cholinergic receptors in either of these disease states.
