Parallel changes in brain flunitrazepam binding and density of noradrenergic innervation.

The neonatal injection of neurotoxic compounds such as 6-hydroxydopa (6-OH-DOPA) and DSP 4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride) produces marked changes in the development of central noradrenergic neurons, i.e. permanent denervation of the cerebral cortex and hyperinnervation of the brain stem and the cerebellum. Adult animals treated at birth with both neurotoxins were used to study the binding of [3H]flunitrazepam (FNZ) to membranes isolated from these regions. The administration of both toxins produced a marked and similar increase in the number of FNZ binding sites in the cerebellum. In the brain stem, 6-OH-DOPA increased the density of these receptors much more than DSP 4 (33% vs. 13%), a difference similar to that observed between the effects of both compounds on brain stem NA. In the cerebral cortex, both compounds reduced the maximal number of FNZ binding sites. No changes were observed in the affinity of FNZ binding sites in the different structures. When adult rats treated at birth with 6-OH-DOPA received an injection of DSP 4 7 days later, the number of FNZ binding sites was reduced by 43% in the cerebellum, 53% in the brain stem and 11% in the cerebral cortex. In these structures, DSP 4 reduced the absolute number of FNZ binding sites to the same level both in rats treated at birth with 6-OH-DOPA and in non-treated animals receiving DSP 4 7 days before killing. These results are further support for the existence of close parallelism between the density of benzodiazepine receptors, as demonstrated by FNZ binding, and the density of brain noradrenergic innervation.