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Noradrenergic neurons lesion as neonates and central histaminergic system activity in adult rats

Przemysław Nowak 1Ryszard Szkilnik 1Adam Kwieciński 1Krystyna Żwirska-Korczala 2Jerzy Jochem 2Łukasz Noras 2Richard M. Kostrzewa 3Ryszard Brus 1

1. Department of Pharmacology, Medical University of Silesia, H. Jordana 38, Zabrze 41-808, Poland
2. Department of Physiology, Medical University of Silesia, H. Jordana 38, Zabrze 41-808, Poland
3. Quillen College of Medicine, East Tennessee State University, Johnson City 37614, United States


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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Presentation: Poster at Zjazd Polskiego Towarzystwa Biochemicznego, Sympozjum V, by Ryszard Szkilnik
See On-line Journal of Zjazd Polskiego Towarzystwa Biochemicznego

Submitted: 2007-04-24 11:04
Revised:   2009-06-07 00:44