Evaluation of the elevated plus-maze and open-field tests for the assessment of anxiety-related behaviour in inbred mice

Carola, Valeria; D’Olimpio, Francesca; Brunamonti, Emiliano; Mangia, Franco; Renzi, Paolo

doi:10.1016/s0166-4328(01)00452-1

Cited by 618 publications

(415 citation statements)

References 33 publications

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“…We also analysed locomotor activity in the open-field test, with the level of activity in the centre of the open field being inversely related to anxiety level [27][28][29] . The distance travelled in the central zone was decreased after acute or chronic stress in WT mice, and this effect was again more pronounced in D2R À / À mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

Role of dopamine D2 receptors in plasticity of stress-induced addictive behaviours

et al. 2013

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Dopaminergic systems are implicated in stress-related behaviour. Here we investigate behavioural responses to chronic stress in dopamine D2 receptor knockout mice and find that anxiety-like behaviours are increased compared with wild-type mice. Repeated stress exposure suppresses cocaine-induced behavioural sensitization, cocaine-seeking and relapse behaviours in dopamine D2 receptor knockout mice. Cocaine challenge after drug withdrawal in cocaine-experienced wild-type or dopamine D2 receptor knockout mice is associated with inhibition of long-term depression in the nucleus accumbens, and chronic stress during withdrawal prevents inhibition after cocaine challenge in cocaine-experienced dopamine D2 receptor knockout mice, but not in wild-type mice. Lentiviral-induced knockdown of dopamine D2 receptors in the nucleus accumbens of wild-type mice does not affect basal locomotor activity, but confers stress-induced inhibition of the expression of cocaine-induced behavioural sensitization. Stressed mice depleted of dopamine D2 receptors do not manifest long-term depression inhibition. Our results suggest that dopamine D2 receptors have roles in regulating synaptic modification triggered by stress and drug addiction.

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Section: Resultsmentioning

confidence: 99%

Role of dopamine D2 receptors in plasticity of stress-induced addictive behaviours

et al. 2013

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“…Variables, related to animal subjects, that need to be considered when setting up an experiment using the elevated plus maze include: strain [66][67][68][69][70] (which may be particularly true when considering mouse background strain when using transgenic models), breeding line differences 71 , sex/gender 22,72,73 , estrous cycle 22,74,75 and age 14,51,76 .…”

Section: Methodsmentioning

confidence: 99%

The use of the elevated plus maze as an assay of anxiety-related behavior in rodents

2007

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The elevated plus maze is a widely used behavioral assay for rodents and it has been validated to assess the anti-anxiety effects of pharmacological agents and steroid hormones, and to define brain regions and mechanisms underlying anxiety-related behavior. Briefly, rats or mice are placed at the junction of the four arms of the maze, facing an open arm, and entries/duration in each arm are recorded by a video-tracking system and observer simultaneously for 5 min. Other ethological parameters (i.e., rears, head dips and stretchedattend postures) can also be observed. An increase in open arm activity (duration and/or entries) reflects anti-anxiety behavior. In our laboratory, rats or mice are exposed to the plus maze on one occasion; thus, results can be obtained in 5 min per rodent. INTRODUCTIONThe elevated plus maze has been described as a simple method for assessing anxiety responses of rodents by File and co-workers 1 . A task, using a Y-shaped apparatus that included an elevated open alley, which produced a strong approach-avoidance conflict, and an enclosed alley, which did not, was first described by Montgomery 2 . This task was modified into an elevated maze with four arms (two open and two enclosed) that are arranged to form a plus shape and was described by Handley and Mithani 3 . These authors described the assessment of anxiety behavior of rodents by using the ratio of time spent on the open arms to the time spent on the closed arms. Unlike other behavioral assays used to assess anxiety responses that rely upon the presentation of noxious stimuli (i.e., electric shock, food/water deprivation, loud noises, exposure to predator odor, etc.) that typically produce a conditioned response, the elevated plus maze relies upon rodents' proclivity toward dark, enclosed spaces (approach) and an unconditioned fear of heights/open spaces (avoidance) 4 .There is great diversity in possible applications of the elevated plus maze. To name a few, prescreening of newly developed pharmacological agents for treatment of anxiety-related disorders can be carried out. The anxiolytic and anxiogenic effects of pharmacological agents, drugs of abuse and hormones can be investigated. The effects of reproductive senescence/aging and/or pre-, peri-or postnatal exposure to various stressors can be assessed. Furthermore, beyond its utility as a model to detect anxiolytic effects of benzodiazepine-related compounds, the elevated plus maze can be used as a behavioral assay to study the brain sites (e.g., limbic regions, hippocampus, amygdala, dorsal raphe nucleus, etc. 5,6 ) and mechanisms (e.g., GABA, glutamate, serotonin, hypothalamic-pituitary-adrenal axis neuromodulators, etc. 1,3,[7][8][9][10][11][12] ) underlying anxiety behavior. Indeed, the elevated plus maze has been used as a model of state, unconditioned anxiety for over two decades, and there are now over 2,000 papers related to this topic. Because a lengthy discussion of these key findings is beyond the scope of this protocol, readers are referred to several excellent an...

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“…The latency time for their first passage from the light compartment to the dark one, the number of entries into each compartment, the time spent in the illuminated area, and the number of times that the mouse reared on its hindpaws in the light space (rearing), were recorded for 5 min (Crawley and Goodwin, 1980 Locomotor and anxiolytic-like activities. The openfield test is a classical system that is routinely used to evaluate general locomotor activity and anxietyrelated behaviour of animals (Ramos and Mormede, 1998;Carola et al, 2002;Prut and Belzung, 2003). This paradigm mimics the natural conflict in mice between their tendencies to explore a novel environment and to avoid an open area (Crawley, 1985;Asano, 1986).…”

Section: Anxiolytic-like Activitymentioning

confidence: 99%

“…rearing) in the central and peripheral zone were recorded automatically (software settings: box size: 4; ambulatory trigger: 2; resting delay: 1500 ms) (Karl et al, 2006). The time spent in the central area, and the ambulation time and vertical activity in this zone, are indicators of the emotional reactivity of the mouse, as the central area of a novel environment is anxiogenic and aversive (Denenberg, 1969;Carola et al, 2002;Meyer et al, 2006). Therefore, these were taken as measures of anxiety.…”

Section: Anxiolytic-like Activitymentioning

confidence: 99%

Adaptogenic and central nervous system effects of single doses of 3% rosavin and 1% salidroside Rhodiola rosea L. extract in mice

Perfumi

Mattioli

2006

Phytotherapy Research

156

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Rhodiola rosea L., or 'golden root', is a popular plant in traditional medicine in Eastern Europe and Asia, with a reputation for improving depression, enhancing work performance, eliminating fatigue and treating symptoms of asthenia subsequent to intense physical and psychological stress. Due to these therapeutic properties, R. rosea is considered to be one of the most active adaptogenic drugs. To confirm and extend results obtained in the few preclinical and clinical studies available in English language journals, the purpose of the present study was to re-investigate the effects produced by a single oral administration of an R. rosea hydroalcohol extract (containing 3% rosavin and 1% salidroside) on the central nervous system in mice. The extract was tested on antidepressant, adaptogenic, anxiolytic, nociceptive and locomotor activities at doses of 10, 15 and 20 mg/kg, using predictive behavioural tests and animal models. The results show that this R. rosea extract significantly, but not dose-dependently, induced antidepressant-like, adaptogenic, anxiolytic-like and stimulating effects in mice. This study thus provides evidence of the efficacy of R. rosea extracts after a single administration, and confirms many preclinical and clinical studies indicating the adaptogenic and stimulating effects of such R. rosea extracts. Moreover, antidepressant-like and anxiolytic-like activities of R. rosea were shown in mice for the first time.

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Evaluation of the elevated plus-maze and open-field tests for the assessment of anxiety-related behaviour in inbred mice

Cited by 618 publications

References 33 publications

Role of dopamine D2 receptors in plasticity of stress-induced addictive behaviours

Role of dopamine D2 receptors in plasticity of stress-induced addictive behaviours

The use of the elevated plus maze as an assay of anxiety-related behavior in rodents

Adaptogenic and central nervous system effects of single doses of 3% rosavin and 1% salidroside Rhodiola rosea L. extract in mice

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