Localization of benzodiazepine-like molecules in the rat brain. A light and electron microscopy immunocytochemistry study with an anti-benzodiazepine monoclonal antibody.

The anti-benzodiazepine (BZD) monoclonal antibody 21-7F9 was used with light and electron microscopy immunocytochemistry techniques for studying the distribution of BZD-like molecules in the rat brain. With light microscopy, BZD-like immunoreactivity was found throughout the brain, mainly in neurons and occasionally in some glial cells (in periventricular areas, as well as in some perivascular astrocytes). Despite the fact that in the cerebellum the GABAergic neurons exhibit BZD-like immunoreactivity, co-localization of these two molecules is not exact, since there are also BZD-like positive neurons that are non-GABAergic (e.g., cerebellar granule cells, some neocortical and hippocampal pyramidal cells). Ultrastructural study of the cerebellar cortex disclosed that all neuronal categories were immunoreactive, as were some astrocytes within the granular layer. The reaction product was concentrated in neuronal perikarya and dendritic processes. Axons and axon terminals remained mostly unlabeled. The absence of immunoprecipitate within cytoplasmic organelles (Golgi apparatus, mitochondria, lumen of endoplasmic reticulum) and its presence at the cytoplasmic face of the cell membranes strongly suggests that endogenous BZD-like molecules are present in both the soluble cytoplasm (hyatoplasm), and also in association with both external and internal cell membranes. The results suggest that the brain BZD-like molecules might be functionally involved in either the modulation of GABA neurotransmission and/or the biotransformation, accumulation and elimination of benzodiazepines and benzodiazepine-like molecules in the brain.