DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] is a neurotoxin which induces acute and selective degeneration of both central and peripheral noradrenergic nerve terminals in mammals. In rats, DSP-4 crosses the blood-brain barrier and produce long-lasting degeneration of the central noradrenergic neurons. Previously we showed that DSP-4 injected on the day 1st and 3rd of life of rats dramatically decreased noradrenaline (NA) level in the brain and modified function of the central serotoninergic, dopaminergic and GABA-ergic neurotransmitter systems in adult animals. The aim of this study was to examine effect of DSP-4 applied to newborn rats on the central histaminergic system in adult rats examined by biochemical and behavioral methods.

Newborn Wistar rats were injected with DSP-4 at 50.0 mg/kg sc twice, on the day 1st and 3rd of postnatal life. Control newborn rats were injected with saline. When rats attained age of 8 weeks the level of NA was assayed in different parts of the brain (HPLC/ED). Beside the content of histamine (H) the brain was estimated by immunoenzymatic method. Then in a separate group of adult male rats with neonatally lesioned central noradrenergic system and control, several behavioral tests were performed. For this study three histamine receptor antagonists were used such as: S(+)chlorpheniramine (for H₁), cimetidine (for H₂) and thioperamide (for H₃). It was shown that neonatal lesion of the central noradrenergic neurons significantly decreased H level in the frontal cortex, and changed the central histamine receptors reactivity to antagonists (mainly H₂ and H₃) examined by behavioral methods in adult rats.

This study was supported by Medical University of Silesia (2007).

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