The relationship of benzodiazepine binding sites to the norepinephrine projection in the hypothalamus of the adult rat

Abstract

The relationship of benzodiazepine binding sites to noradrenergic terminals in different brain regions of adult rats was evaluated. The in vitro addition of 10(-5) M diazepam (DZ) significantly reduced the depolarization-induced release of [3H]norepinephrine (NE) in the hypothalamus, while no effect was observed in the cerebellum, suggesting that DZ may act directly on NE terminals in the hypothalamus. The action of DZ in the hypothalamus was blocked either by co-incubation with the benzodiazepine (BZ) antagonist RO 15-1788 (a neutral ligand for BZ binding sites) or with the GABA antagonist, bicuculline. Analysis of BZ binding heterogeneity, using the triazolopyridazine CL 218,872 as displacing agent, indicated that binding heterogeneity exists in both the cortex and hypothalamus, whereas the cerebellum has a more homogeneous binding site population. Binding site heterogeneity does not appear to explain the selective effect of DZ on hypothalamic noradrenergic terminals. Systemic injection of the neurotoxin 6-hydroxyDOPA decreased NE levels significantly in the cerebellum, cortex and hypothalamus. Only in the hypothalamus, however, did the decrease in NE levels correlate in magnitude with the decrease in BZ receptor binding. A large proportion of BZ receptors may be located presynaptically on the hypothalamic NE terminals. The location of these BZ binding sites may contribute to the unique response to DZ observed in the hypothalamus following either in vitro or in utero exposure.