Modification of the Effects of Benzodiazepines on the Exploratory Behaviors of Mice on a Hole-Board by Diabetes

Kamei, Junzo; Ohsawa, Masahiro; Tsuji, Minoru; Takeda, Hiroshi; Matsumiya, Teruhiko

doi:10.1254/jjp.86.47

Cited by 34 publications

(23 citation statements)

References 25 publications

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“…)-treated mice is likely to be reflected in the hypolocomotor activity. We previously reported that diazepam at 0.3 mg / kg exerted the significant anxiolytic-like effect in the mouse hole-board test (20). Therefore, the freezing behavior in the elevated openplatform test may not be affected by diazepam at the dose having no effect on locomotor activity.…”

Section: Resultsmentioning

confidence: 95%

Effects of Serotonergic Anxiolytics on the Freezing Behavior in the Elevated Open-Platform Test in Mice

et al. 2007

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Abstract. Freezing behavior is thought to be a sign of fear in animals. We examined whether the freezing behavior during the elevated open-platform stress, which is a psychological stressor without painful stimulus, is modulated by serotonergic neurotransmission and would be a useful marker for screening anxiolytic and / or antidepressant. Male ICR mice (6 -8-week-old) were individually placed on an elevated open-platform and the duration of freezing behavior of mouse was measured for 10 min. Fluoxetine and citalopram, selective serotonin (5-HT) reuptake inhibitors, markedly decreased the duration of freezing. Fenfluramine, a 5-HT releaser, and 8-OH-DPAT, a potent 5-HT 1A -receptor agonist, also significantly decreased the duration of freezing. In contrast, the 5-HT-synthesis inhibitor p-chlorophenylalanine significantly increased the duration of freezing. Diazepam, a benzodiazepine anxiolytic, had no effect on the duration of freezing at doses having no effect on locomotor activity. Imipramine and clomipramine, tricyclic antidepressants, also did not affect the duration of freezing. Reboxetine, a selective noradrenaline reuptake inhibitor, significantly increased the duration of freezing. These results indicate that the activation of serotonergic neurotransmission attenuates the fear-related behavior in the elevated open-platform test, while the activation of noradrenergic neurotransmission increases the fearrelated behavior. In addition, this test is convenient for assaying anxiolytic drugs that affect serotonergic neurotransmission.

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Section: Resultsmentioning

confidence: 95%

Effects of Serotonergic Anxiolytics on the Freezing Behavior in the Elevated Open-Platform Test in Mice

et al. 2007

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“…Guyot et al (27) indicated that chronic hyperglycemia reduces extracellular GABA levels. Furthermore, we previously reported that the anxiolytic effect of diazepam in an unfamiliar environment was decreased by diabetes in mice (28). Therefore, it is possible that the decreased efficacy of pentobarbital in diabetic mice may be due, at least in part, to the changes in GABAergic systems.…”

Section: Discussionmentioning

confidence: 98%

Effects of First- and Second-Generation Histamine-H1-Receptor Antagonists on the Pentobarbital-Induced Loss of the Righting Reflex in Streptozotocin-Induced Diabetic Mice

et al. 2005

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Abstract. The second-generation histamine-H 1 -receptor antagonists, such as epinastine and cetirizine, are used as non-sedating antihistamines for treating allergic symptoms due to their poor ability to penetrate blood-brain barrier. Because it has been reported that the blood-brain barrier system is disturbed in diabetes, it is possible that second-generation histamine-H 1 -receptor antagonists may easily penetrate the blood-brain barrier and cause potent sedation in diabetics. In the present study, we investigated the effects of first-generation (diphenhydramine) and second-generation (epinastine and cetirizine) histamine-H 1 -receptor antagonists on the duration of pentobarbital-induced loss of the righting reflex (LORR) in non-diabetic and diabetic mice. Systemic treatment with diphenhydramine (3 -30 mg / kg, s.c.), and intracerebroventricular treatment with epinastine (0.03 -0.3 mg / mouse) and cetirizine (0.03 -0.3 mg/ mouse) dose-dependently and significantly increased the duration of pentobarbital-induced LORR in both nondiabetic and diabetic mice. Although systemic treatment with epinastine (3 -30 mg / kg, s.c.) and cetirizine (3 -30 mg / kg, s.c.) did not affect the duration of pentobarbital-induced LORR in nondiabetic mice, these treatments significantly prolonged it in diabetic mice. Our results suggest that the systemic administration of second-generation histamine-H 1 -receptor antagonists may produce a central nervous system depressant effect in diabetes.

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“…In the present study, we subjected 4-week-old mice to OBX and the behavioral test was performed 2 weeks after surgery, since in general the hole-board test is used in 6-week-old mice (17,19,20). Mice were anesthetized with sodium pentobarbital (50 mg / kg, i.p.)…”

Section: Obxmentioning

confidence: 99%

Changes in Emotional Behavior of Mice in the Hole-Board Test After Olfactory Bulbectomy

et al. 2006

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Abstract. The most consistent behavioral change caused by olfactory bulbectomy (OBX) is a hyperemotional response to novel environmental stimuli. The aim of this study was to characterize the emotional behavior of OBX mice using the hole-board test. After the olfactory bulbs were lesioned, sham and OBX mice were housed in single cages for 14 days. The number of head-dips in the hole-board test in single-housed OBX mice was significantly greater than that in single-housed sham mice. The head-dipping behaviors in single-housed sham and OBX mice were reversed by treatment with diazepam, a typical benzodiazepine anxiolytic. (±)-8-Hydroxy-2-(di-n-propylamino) tetraline hydrobromide (8-OH-DPAT), a selective 5-HT 1A -receptor agonist that has a non-benzodiazepine anxiolytic-like effect, and (+)-4-[(aR)-a-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethyl benzamide (SNC80), a δ-opioid-receptor agonist, also significantly reversed the number of head-dips in single-housed sham and OBX mice. In conclusion, we suggest that the single-housed OBX mice showed heightened emotional behavior (e.g., increase in head-dipping behavior) in the hole-board test. In addition, we suggest that the hyperemotional behavior characterized by head-dipping behavior in OBX mice was selectively reversed by benzodiazepine and non-benzodiazepine anxiolytics.

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Modification of the Effects of Benzodiazepines on the Exploratory Behaviors of Mice on a Hole-Board by Diabetes

Cited by 34 publications

References 25 publications

Effects of Serotonergic Anxiolytics on the Freezing Behavior in the Elevated Open-Platform Test in Mice

Effects of Serotonergic Anxiolytics on the Freezing Behavior in the Elevated Open-Platform Test in Mice

Effects of First- and Second-Generation Histamine-H1-Receptor Antagonists on the Pentobarbital-Induced Loss of the Righting Reflex in Streptozotocin-Induced Diabetic Mice

Changes in Emotional Behavior of Mice in the Hole-Board Test After Olfactory Bulbectomy

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