Neurotransmitter receptor localizations: brain lesion induced alterations in benzodiazepine, GABA, beta-adrenergic and histamine H1-receptor binding.

Selective neuronal lesions have been utilized in efforts to localize binding sites in rat brain for beta-adrenergic, gamma-aminobutyric acid (GABA), histamine H1 and benzodiazepine receptors. The various receptors respond differentially to lesions both in extent of change and in time course. After kainate lesions in the corpus striatum, benzodiazepine receptors are depleted up to 45% at 45--78 days but are unaffected after 7 days. By contrast striatal GABA receptors are increased at 7 days but depleted at later times. Thus both striatal benzodiazepine and GABA receptors appear to be associated at least in part with intrinsic neurons. In the cerebellum both benzodiazepine and GABA receptors are reduced in kainate treated rats and in Nervous mice, mutants which lack Purkinje cells. The most pronounced dissimilarity between benzodiazepine and GABA receptors occurs in Weaver mice, which selectively lack granule cells and display a 60% reduction in GABA receptors but a 40% augmentation in benzodiazepine receptors. A major portion of cerebellar GABA receptors, therefore, appear to be localized to granule cells. Striatal beta-adrenergic receptors are reduced following intrastriatal kainate injections but are unaffected by cerebral cortex ablation, suggesting an association with intrinsic neurons but not with axon terminals of the corticostriate pathway. While intraventricular injections of 6-hydroxydopamine enhance [3H]dihydroalprenolol binding to beta-adrenergic receptors in the cerebral cortex and hippocampus, such binding is not augmented in the corpus striatum, brain stem, midbrain or thalamus-hypothalamus by this treatment. Moreover, medial forebrain bundle lesions, which destroy ascending adrenergic neurons, fail to alter cerebral cortical or striatal beta-adrenergic receptors. Thus denervation-elicited increases in beta-adrenergic receptors vary with brain region and the type of denervating lesion. Histamine H1-receptors are the most resistant of all to neuronal lesions. In the corpus striatum [3H]mepyramine binding is unaffected by cerebral cortex ablation, nigral injections of 6-hydroxydopamine or brain stem hemisection. In the hippocampus, medial forebrain bundle lesions, intrahippocampal kainate injection, and fimbria and fornix transection largely fail to alter [3H]mepyramine binding. Accordingly, a major portion of these receptors may be associated with nonneuronal elements such as glia or blood vessels.