title: Predicting anxiety responses to halogenated glucocorticoid drugs using the hexobarbital sleep time test.
abstract: Glucocorticoids (GCs) are used to treat numerous diseases, but their use in limited by adverse side effects. One such effect is occasional increased anxiety. Since the intensity of hepatic microsomal oxidation has been shown to alter responses to GC, we examined the possibility that rats with lower rates of hepatic GC metabolism would have increased anxiety. We hypothesized that the resulting, excessive GC would stimulate brain monoamine oxidase A (MAO-A), which would reduce brain serotonin, and thereby increase anxiety. Hepatic microsomal oxidative intensity was evaluated by the hexobarbital sleep time (HST) test. Results showed that rats with lower rates of hepatic GC metabolism had elevated brain MAO-A activity, reduced brain serotonin, and more anxiety than rats with higher rates of hepatic GC metabolism. We suggest that the HST test, as an integrative test of microsomal oxidation status, should be useful for predicting individual sensitivity to GC and to other drugs metabolized by the hepatic microsomal oxidation system.
authors.affiliation: a High Biomedical School , South Ural State University , Chelyabinsk , Russia ;
authors.forename: Olga B
authors.initials: OB
authors.lastname: Tseilikman
authors.affiliation: a High Biomedical School , South Ural State University , Chelyabinsk , Russia ;|b Department of Biochemistry , South Ural State Medical University , Chelyabinsk , Russia ;
authors.forename: Denis A
authors.initials: DA
authors.lastname: Kozochkin
authors.affiliation: c Institute of General Pathology and Pathophysiology , Moscow , Russia ;|d University of North Texas Health Science Center , Fort Worth , USA ;
authors.forename: Eugenia B
authors.initials: EB
authors.lastname: Manukhina
authors.affiliation: d University of North Texas Health Science Center , Fort Worth , USA ;
authors.forename: H Fred
authors.initials: HF
authors.lastname: Downey
authors.affiliation: b Department of Biochemistry , South Ural State Medical University , Chelyabinsk , Russia ;
authors.forename: Maria E
authors.initials: ME
authors.lastname: Misharina
authors.affiliation: a High Biomedical School , South Ural State University , Chelyabinsk , Russia ;|b Department of Biochemistry , South Ural State Medical University , Chelyabinsk , Russia ;
authors.forename: Maria V
authors.initials: MV
authors.lastname: Komelkova
authors.affiliation: a High Biomedical School , South Ural State University , Chelyabinsk , Russia ;|b Department of Biochemistry , South Ural State Medical University , Chelyabinsk , Russia ;
authors.forename: Anna A
authors.initials: AA
authors.lastname: Nikitina
authors.affiliation: b Department of Biochemistry , South Ural State Medical University , Chelyabinsk , Russia ;
authors.forename: Svyatoslav V
authors.initials: SV
authors.lastname: Golodnii
authors.affiliation: e Department of Biochemistry, Rostov State Medical University , Rostov on Don , Russia.
authors.forename: Margarita A
authors.initials: MA
authors.lastname: Dodohova
authors.affiliation: a High Biomedical School , South Ural State University , Chelyabinsk , Russia ;|b Department of Biochemistry , South Ural State Medical University , Chelyabinsk , Russia ;
authors.forename: Vadim E
authors.initials: VE
authors.lastname: Tseilikman
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005938:Glucocorticoids / Q000493:pharmacokinetics*; D006591:Hexobarbital; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D008995:Monoamine Oxidase / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005938:Glucocorticoids; D003577:Cytochrome P-450 Enzyme System; D006591:Hexobarbital; D008995:Monoamine Oxidase
keywords: Anxiety; cytochrome P450; glucocorticoids; hexobarbital; monoamine oxidase A; serotonin