Effects of valproate and lorazepam on experimental anxiety: Tolerance, withdrawal, and role of clonidine

Angelis, L. de

doi:10.1016/0091-3057(95)00100-b

Cited by 24 publications

(19 citation statements)

References 20 publications

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“…The lack of drug effect in the light/dark box and the resident-intruder test are in contrast with these hypothesis as well as with previous reports demonstrating anxiolytic effects [imipramine (de Angelis, 1992, 1995); valproate (Yoshimura and Ogawa, 1984; Ibarguen-Vargas et al, 2009)] and anti-aggressive effects [imipramine (Pinna et al, 2004); valproate (Einat, 2007b); lithium (Wei et al, 2007; Uchida et al, 2009; Veenema, 2009; Veenema and Neumann, 2009)] in these tests. The lack of effects in the resident-intruder test could be at least partially explained by the low baseline aggression found in Stage 2 of the present study, which could have created a floor effect masking possible drug effects.…”

Section: Discussioncontrasting

confidence: 82%

Strain-specific battery of tests for domains of mania: effects of valproate, lithium and imipramine

Flaisher-Grinberg

Einat

2010

Front. Psychiatry

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The lack of efficient animal models for bipolar disorder (BPD), especially for the manic pole, is a major factor hindering the research of its pathophysiology and the development of improved drug treatments. The present study was designed to identify an appropriate mouse strain for modeling some behavioral domains of mania and to evaluate the effects of drugs using this strain. The study compared the behavior of four strains: Black Swiss, C57Bl/6, CBA/J and A/J mice in a battery of tests that included spontaneous activity; sweet solution preference; light/dark box; resident-intruder; forced-swim and amphetamine-induced hyperactivity. Based on the ‘manic-like’ behavior demonstrated by the Black Swiss strain, the study evaluated the effects of the mood stabilizers valproate and lithium and of the antidepressant imipramine in the same tests using this strain. Results indicated that lithium and valproate attenuate the ‘manic-like’ behavior of Black Swiss mice whereas imipramine had no effects. These findings suggest that Black Swiss mice might be a good choice for modeling several domains of mania and distinguishing the effects of drugs on these specific domains. However, the relevance of the behavioral phenotype of Black Swiss mice to the biology of BPD is unknown at this time and future studies will investigate molecular differences between Black Swiss mice and other strains and asess the interaction between strain and mood stabilizing treatment.

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Section: Discussioncontrasting

confidence: 82%

Strain-specific battery of tests for domains of mania: effects of valproate, lithium and imipramine

Flaisher-Grinberg

Einat

2010

Front. Psychiatry

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“…In summary, anxiolytic effects of lorazepam were successfully antagonized by flumazenil in our study and other anxiety models (13,14). Our study indicated that approximately 60 percent of the anxiolytic action of thymoquinone and -pinene could be accounted for by inhibition of the benzodiazepine pathway.…”

Section: Raza El-hadiyah and Al-shabanah 159supporting

confidence: 43%

Nigella sativaSeed Constituents and Anxiety Relief in Experimental Models

Raza

El-Hadiyah

Al‐Shabanah

2007

Journal of Herbs, Spices & Medicinal Plants

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This study investigated anti-anxiety effects of Nigella sativa seed constituents (aqueous extract, fixed oil, volatile oil, and major constituents of the volatile oil) using male mice and the Y-maze and hole-board tests as models for exploration-induced anxiety and the water-lick test as a model for conflict-induced anxiety. The seed constituents were injected intraperitoneal into male mice and subjected to tests 1 h later. Except for the aqueous extract, all the tested constituents demonstrated an anti-anxiety effect in the Y-maze and hole-board tests. In the water-lick test, all constituents were ineffective in reducing anxiety except for the volatile oil. The failure to demonstrate anxiolytic effects in the water-lick conflict test may be due to this test model representing a more difficult task to the test animals as compared with the other test models. The anxiolytic activity of the volatile oil in the Y-maze and hole-board tests can be attributed to the contents thymoquinone, -pinene, and p-cymene. The α-pinene and p-cymene appear to be excellent anti-anxiety agents in the hole-board test as these compounds did not retard spontaneous locomotor activity in treated animals. Exploration on the mechanism of action using the benzodiazepine antagonist flumazenil suggested that benzodiaz-M. Raza is affiliated with

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“…Lorazepam (100 μg/kg) was diluted in distilled water, which is a good diluent for lorazepam, and an appropriate vehicle control solution (0.9% NaCl) was administered. The dose of lorazepam (100μg/kg/day), was chosen based on prior studies (Miller et al, 1987; de Angelis et al, 1995). A pilot study to determine dose-response in the open field test was also performed at this concentration in our laboratory.…”

Section: Methodsmentioning

confidence: 99%

GABAergic modulation with classical benzodiazepines prevent stress-induced neuro-immune dysregulation and behavioral alterations

Ramírez

Niraula

Sheridan

2016

Brain, Behavior, and Immunity

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Objective Psychosocial stress is associated with altered immunity, anxiety, and depression. Repeated social defeat (RSD), a model of social stress, triggers egress of inflammatory myeloid progenitor cells (MPCs; CD11b+ /Ly6Chi) that traffic to the brain, promoting anxiety-like behavior. In parallel, RSD enhances neuroinflammatory signaling and long-lasting social avoidant behavior. Lorazepam and clonazepam are routinely prescribed anxiolytics that act by enhancing GABAergic activity in the brain. Besides binding to the central benzodiazepine binding site (CBBS) in the central nervous system (CNS), lorazepam binds to the translocator protein (TSPO) with high affinity causing immunomodulation. Clonazepam targets the CBBS and has low affinity for the TSPO. Here the aims were to determine if lorazepam and clonazepam would: 1) prevent stress-induced peripheral and central inflammatory responses, and 2) block anxiety and social avoidance behavior in mice subjected to RSD. Methods C57/BL6 mice were divided into experimental groups, and treated with either lorazepam (0.10mg/kg), clonazepam (0.25 mg/kg) or vehicle (0.9%NaCl). Behavioral data and tissues were collected the morning after the last cycle of RSD. Results Lorazepam and clonazepam were effective in attenuating mRNA expression of CRH in the hypothalamus and corticosterone in plasma in mice subjected to RSD. Both drugs blocked stress-induced levels of IL-6 in plasma. Lorazepam and clonazepam had different effects on stress-induced enhancement of myelopoiesis and inhibited trafficking of monocytes and granulocytes in circulation. Furthermore, lorazepam, but not clonazepam, inhibited splenomegaly and the production of pro-inflammatory cytokines in the spleen following RSD. Additionally, lorazepam and clonazepam, blocked stress-induced accumulation of macrophages (CD11b+/CD45high) in the CNS. In a similar manner, both lorazepam and clonazepam prevented neuroinflammatory signaling and reversed anxiety-like and depressive-like behavior in mice exposed to RSD. Conclusion These data support the notion that lorazepam and clonazepam, aside from exerting anxiolytic and antidepressant effects, may have therapeutic potential as neuroimmunomodulators during psychosocial stress. The reversal of RSD-induced behavioral outcomes may be due to the enhancement of GABAergic neurotransmission, or some other off-target effect. The peripheral actions of lorazepam, but not clonazepam, seem to be mediated by TSPO activation.

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Effects of valproate and lorazepam on experimental anxiety: Tolerance, withdrawal, and role of clonidine

Cited by 24 publications

References 20 publications

Strain-specific battery of tests for domains of mania: effects of valproate, lithium and imipramine

Strain-specific battery of tests for domains of mania: effects of valproate, lithium and imipramine

Nigella sativaSeed Constituents and Anxiety Relief in Experimental Models

GABAergic modulation with classical benzodiazepines prevent stress-induced neuro-immune dysregulation and behavioral alterations

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