To study the influence of the central noradrenergic system on sensitivity to sedative-hypnotic effects mediated by the aminobutyric acid (GABA) system, intact rats were contrasted with rats in which noradrenergic nerves were largely destroyed shortly after birth with the neurotoxin DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine; 50 mg/kg sc x2, P1 and P3]. At 10 weeks, loss of the righting reflex (LORR) was used as an index to study the acute sedative-hypnotic effects of phenobarbital (100 mg/kg ip) and ethanol (4 g/kg ip, 25% v/v). Additionally, GABA concentration in the medial prefrontal cortex (PFC), hippocampus, cerebellum and brainstem was estimated by an HPLC/ED method. Neonatal DSP-4 treatment diminished the sedative-hypnotic effects of both phenobarbital and ethanol in adult rats. While the endogenous GABA content in the PFC, hippocampus, brainstem and cerebellum of DSP-4-treated rats was not altered, phenobarbital significantly decreased GABA content of both intact and DSP-4-lesioned rats by ∼40% in the hippocampus and by ∼20% in other brain regions at 1 h. Ethanol reduced GABA content by ∼15-30% but only in the hippocampus and brainstem of both intact and lesioned rats. These findings indicate that the noradrenergic system exerts a prominent influence on sedative-hypnotics acting via GABAergic systems in the brain without directly altering GABA levels in the brain.
Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-18954 |
Date | 19 August 2008 |
Creators | Bortel, Aleksandra, Słomian, Lucyna, Nitka, Dariusz, Świerszcz, Michał, Jaksz, Mirella, Adamus-Sitkiewicz, Beata, Nowak, Przemysław, Jośko, Jadwiga, Kostrzewa, Richard M., Brus, Ryszard |
Publisher | Digital Commons @ East Tennessee State University |
Source Sets | East Tennessee State University |
Detected Language | English |
Type | text |
Source | ETSU Faculty Works |
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