Co-Administration of Subeffective Anxiolytic Doses of Diazepam and Hydroxyzine in Elevated Zero-Maze in Mice
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Objective Benzodiazepines are from the most common drugs which are used for treatment of anxiety disorders. There are other drugs with antianxiety properties including antihistamines such as hydroxyzine, too. Body of evidence show that co-administration of two drugs which act through different mechanisms, makes the dose of each drug to be reduced, while preserving the desired effect with less adverse drug reactions. The aim of this study was to see whether co-administration of subeffective antianxiety doses of diazepam and hydroxyzine has any antianxiety effect in elevated zero-maze (EZM) in mice. Methods To find the highest subeffective dose of each drug, different doses of hydroxyzine from 1.5 to 24 mg/kg and diazepam in doses of 0.25, 0.5 and 1 mg/kg were injected to male mice. Thirty minutes later, the animals were placed on EZM and various parameters of an-xiety were recorded by a camera to assess later. After determination of subeffective antianxiety dose of the drugs, co-administration of hydroxyzine and diazepam was done and the anxiety parameters were measured. Results In co-administration of 0.25 mg/kg of diazepam and 12 mg/kg hydroxyzine, as subeffective antianxiety doses of either drug, there were not any significant differences in main anxiety parameters, i.e., time spent in open areas and open area entries compared to control group. Hence, no anxiolytic effect was seen. Conclusion It seems that subeffective doses of diazepam and hydroxyzine may not have any facilitating or synergistic effect on each other in antianxiety responses in mice.
Abstract
Objective Benzodiazepines are from the most common drugs which are used for treatment of anxiety disorders. There are other drugs with antianxiety properties including antihistamines such as hydroxyzine, too. Body of evidence show that co-administration of two drugs which act through different mechanisms, makes the dose of each drug to be reduced, while preserving the desired effect with less adverse drug reactions. The aim of this study was to see whether co-administration of subeffective antianxiety doses of diazepam and hydroxyzine has any antianxiety effect in elevated zero-maze (EZM) in mice. Methods To find the highest subeffective dose of each drug, different doses of hydroxyzine from 1.5 to 24 mg/kg and diazepam in doses of 0.25, 0.5 and 1 mg/kg were injected to male mice. Thirty minutes later, the animals were placed on EZM and various parameters of an-xiety were recorded by a camera to assess later. After determination of subeffective antianxiety dose of the drugs, co-administration of hydroxyzine and diazepam was done and the anxiety parameters were measured. Results In co-administration of 0.25 mg/kg of diazepam and 12 mg/kg hydroxyzine, as subeffective antianxiety doses of either drug, there were not any significant differences in main anxiety parameters, i.e., time spent in open areas and open area entries compared to control group. Hence, no anxiolytic effect was seen. Conclusion It seems that subeffective doses of diazepam and hydroxyzine may not have any facilitating or synergistic effect on each other in antianxiety responses in mice.
참고문헌 (20)
- Baldessarini RJ, "Drug Therapy of Depression and Anxiety Disorders, in Goodman and Gilman’s the Pharmacological Basis of Therapeutics", pp.429~459 (2006), McGraw-Hill
- Oates JA, "The Science of Drug Therapy, in Goodman and Gilman’s the Pharmacological Basis of Therapeutics", pp.117~136 (2006), McGraw-Hill
- Xu Z, "Anxiolytic-Like Effect of baicalin and its additivity with other anxiolytics", Planta Med, 72, pp.189~192 (2006)
- Massé F, "Anxiolytic-like effect of 5-HT(2) ligands and benzodiazepines co-administration: comparison of two animal models of anxiety (the four-plate test and the elevated plus maze)", Behav Brain Res, 177, pp.214~226 (2007)
- Poleszak E, "Benzodiazepine", GABA(A) receptors are involved in magnesium-induced anxiolytic-like behavior in mice, 2008, pp.60, 483~489
- Shepherd JK, "Behavioural and pharmacological characterisation of the elevated “zero-maze” as an animal model of anxiety", Psychopharmacology, 116, pp.56~64 (1994)
- Gladney M, "Anxiolytic activity of chloral hydrate and hydroxyzine", Pediatr Dent, 16, pp.183~189 (1994)
- Yamamoto T, "Behavioral analysis of zopiclone on the basis of their discriminative stimulus properties in the rat", Jpn J Pharmacol, 51, pp.337~345 (1989)
- Martin P, "Effects of co-administration of an antidepressant and an anxiolytic drug in the “learned helplessness” paradigm: importance of hydroxyzine", Encephale, 22, pp.270~279 (1996)
- Frances H, "Isolation-induced social behavioral deficit test: effect of tranquillizing drugs", Pharmacol Biochem Behav, 34, pp.293~296 (1989)
- Consoli D, "Behavioral effects of the β3 adrenoceptor agonist SR58611A: is it the putative prototype of a new class of antidepressant", anxiolytic drugs, 2007, pp.573, 139~147
- Silva MI, "Central nervous system activity of acute administration of isopulegol in mice", Pharmacol Biochem Behav, 88, pp.141~147 (2007)
- Luuk H, "Wfs1-deficient mice display impaired behavioural adaptation in stressful environment", Behav Brain Res, 198, pp.334~345 (2009)
- Raud S, "Targeted mutation of CCK2 receptor gene modifies the behavioural effects of diazepam in female mice", Psychopharmacology, 168, pp.417~425 (2003)
- Ognibene E, "Behavioral effects of 6-bromoflavanone and 5-methoxy-6,8-dibromoflavanone as anxiolytic compounds", Prog Neuropsychopharmacol Biol Psychiatry, 32, pp.128~134 (2008)
- Gupta GL, "Effect of Withania somnifera Dunal in ethanol-induced anxiolysis and withdrawal anxiety in rats", Indian J Exp Biol, 464, pp.470~475 (2008)
- Belzung C, "Naloxone potentiates the effects of subeffective doses of anxiolytic agents in mice", Eur J Pharmacol, 323, pp.133~136 (1997)
- Pasricha PJ, "Treatment of Disorders of Bowel Motility and Water Flux; Antiemetics; Agents Used in Biliary and Pancreatic Disease, in Goodman and Gilman’s the Pharmacological Basis of Therapeutics", pp.983~1008 (2006), McGraw-Hill
- Katzung BG, "Histamine, Serotonin, & the Ergot Alkaloids, in Basic & Clinical Pharmacology", pp.255~276 (2007), McGraw-Hill
- Skidgel RA, "Histamine, Bradykinin and Their Antagonists, in Goodman and Gilman’s the Pharmacological Basis of Therapeutics", pp.629~651 (2006), McGraw-Hill