The interaction between ethanol and pregnanolone at induction of anaesthesia investigated with a threshold method in male rats

Citation
Md. Wang et al., The interaction between ethanol and pregnanolone at induction of anaesthesia investigated with a threshold method in male rats, BR J PHARM, 134(7), 2001, pp. 1393-1402
Citations number
55
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BRITISH JOURNAL OF PHARMACOLOGY
ISSN journal
0007-1188 → ACNP
Volume
134
Issue
7
Year of publication
2001
Pages
1393 - 1402
Database
ISI
SICI code
0007-1188(200112)134:7<1393:TIBEAP>2.0.ZU;2-T
Abstract
1 An anaesthesia threshold was used to investigate the pharmacodynamic and pharmacokinetic interactions between ethanol and pregnanolone in male rats. 2 The criterion to determine threshold doses of pregnanolone was the first burst suppression of 1 s in the EEG. Ethanol (0.5, 1.0, 1.5 and 2.0 g kg(-1 )) was injected i.p. 15 min before pregnanolone infusion. Trunk blood, seru m, cortex, cerebellum, hippocampus, striatum, brain stem, fat and muscle ti ssues obtained at criterion were used to determine ethanol (blood) and preg nanolone. 3 Ethanol reduced threshold doses in a dose dependent linear manner. A simi lar reduction of pregnanolone tissue concentrations was only found in brain stem and striatum. Deviations consisted of larger decreases in serum, cere bellum and hippocampus after 0.5 g kg(-1) ethanol and in cerebellum, cortex and hippocampus after 2.0 g kg(-1) of ethanol. Positive correlations betwe en dose and concentration of pregnanolone was recorded in brain stem, hippo campus, cerebellum and cortex. A kinetic component influenced the concentra tion in cortex. There was a correlation between dose and serum concentratio n of pregnanolone only after ethanol. In the muscle 0.5 g kg(-1) ethanol ha d no influence on pregnanolone concentration. 4 The linear, additive pharmacodynamic interaction could involve the GABA i onophore. A pharmacokinetic interaction was found in cortex. The retained h igh uptake of pregnanolone in muscle (after 0.5 g kg(-1)) corresponded to l osses in other tissues (including serum). The reduced uptake of pregnanolon e in cerebellum, cortex and hippocampus (after 2.0 g kg(-1)) was not due to a corresponding change in serum concentration. It was probably due to a re duced blood flow.