Experimental Models of Anxiety for Drug Discovery and Brain Research

Hart, Peter C.; Bergner, Carisa L.; Smolinsky, Amanda N.; Dufour, Brett D.; Egan, Rupert J.; LaPorte, Justin L.; Kalueff, Allan V.

doi:10.1007/978-1-60761-058-8_18

Cited by 46 publications

(22 citation statements)

References 38 publications

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“…The light/dark box is viewed as an ethological model of anxiety (10), placing into competition the drives to remain safe and to explore novel environments. The apparatus has two compartments (Fig.…”

Section: Behaviormentioning

confidence: 99%

“…Following 2 min of habituation in the dark, a barrier between the two sides was removed, enabling the mouse to explore the light side freely. Light-side exploration is typically reduced in anxious mice (10,16). We held novelty constant by giving all groups the same exposure to the experimental box, so differences among groups following the laser treatment should reflect their relative anxiety.…”

Section: Behaviormentioning

confidence: 99%

“…Because mindfulness meditation has often been associated with reductions in anxiety and negative affect (9), we examined exploratory behavior in the light/dark box. In this ethological model of anxiety, time in the light versus dark sides is thought to be a joint effect of novelty (favoring exploration of the light side) and anxiety (favoring the dark) (10). Novel object and location recognition memory also were tested as a measure of cognitive change (11) because improved attention and memory also have been reported following meditation training (9).…”

mentioning

confidence: 99%

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Rhythmic brain stimulation reduces anxiety-related behavior in a mouse model based on meditation training

Weible

Piscopo

Rothbart

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Meditation training induces changes at both the behavioral and neural levels. A month of meditation training can reduce selfreported anxiety and other dimensions of negative affect. It also can change white matter as measured by diffusion tensor imaging and increase resting-state midline frontal theta activity. The current study tests the hypothesis that imposing rhythms in the mouse anterior cingulate cortex (ACC), by using optogenetics to induce oscillations in activity, can produce behavioral changes. Mice were randomly assigned to groups and were given twenty 30-min sessions of light pulses delivered at 1, 8, or 40 Hz over 4 wk or were assigned to a no-laser control condition. Before and after the month all mice were administered a battery of behavioral tests. In the light/dark box, mice receiving cortical stimulation had more light-side entries, spent more time in the light, and made more vertical rears than mice receiving rhythmic cortical suppression or no manipulation. These effects on light/dark box exploratory behaviors are associated with reduced anxiety and were most pronounced following stimulation at 1 and 8 Hz. No effects were seen related to basic motor behavior or exploration during tests of novel object and location recognition. These data support a relationship between lower-frequency oscillations in the mouse ACC and the expression of anxiety-related behaviors, potentially analogous to effects seen with human practitioners of some forms of meditation.ne month of integrated mind body meditation (1), a form of mindfulness meditation, has been shown to reduce selfreported anxiety as measured by the Profile of Mood States, reduce the stress hormone cortisol, increase ventral anterior cingulate cortex (ACC) activity, and change the white matter pathways surrounding the ACC as measured by increased fractional anisotropy in diffusion tensor imaging studies (1-4). How might a purely mental exercise such as paying attention to the present moment work to produce these changes in behavior and brain connectivity (5)?Some of these changes, including those to white matter, were hypothesized to be related to the finding that meditation can increase frontal theta activity even when the person is at rest (6). The theta activity may increase the number of active oligodendrocytes leading to increased myelination, thereby improving connectivity between the ACC and other limbic areas. Moreover, theta activity in humans has been uniquely correlated with glucose metabolism in the ACC (7). Because the ventral ACC connects to the amygdala and is thought to regulate its activity (8), these changes in the brain could result in the reduced anxiety found following meditation training.To test this idea, we developed a mouse model in which various frequencies of oscillatory activity were induced in the ACC using optogenetics. Because mindfulness meditation has often been associated with reductions in anxiety and negative affect (9), we examined exploratory behavior in the light/dark box. In this ethological model of anxiet...

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Section: Behaviormentioning

confidence: 99%

Section: Behaviormentioning

confidence: 99%

mentioning

confidence: 99%

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Rhythmic brain stimulation reduces anxiety-related behavior in a mouse model based on meditation training

Weible

Piscopo

Rothbart

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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show abstract

“…Ten male Swiss mice from Jackson Laboratories were used in this study housed in groups of 4-6 mice per cage to avoid stress and anxiety induced by social isolation 38 , although some believe individual housing decreases anxiety in mice 13 . The mice were housed in a 12-hour day/night cycle where food was administered Behavioral experiments.…”

Section: Methodsmentioning

confidence: 99%

MATSAP: An Automated Analysis of Stretch-Attend Posture in Rodent Behavioral Experiments

Holly

Murray

2016

2016 32nd Southern Biomedical Engineering Conference (SBEC)

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Stretch-attend posture (SAP) occurs during risk assessment and is prevalent in common rodent behavioral tests. Measuring this behavior can enhance behavioral tests. For example, stretch-attend posture is a more sensitive measure of the effects of anxiolytics than traditional spatiotemporal indices. However, quantifying stretch-attend posture using human observers is time consuming, somewhat subjective, and prone to errors. We have developed MATLAB-based software, MATSAP, which is a quick, consistent, and open source program that provides objective automated analysis of stretchattend posture in rodent behavioral experiments. Unlike human observers, MATSAP is not susceptible to fatigue or subjectivity. We assessed MATSAP performance with videos of male Swiss mice moving in an open field box and in an elevated plus maze. MATSAP reliably detected stretch-attend posture on par with human observers. This freely-available program can be broadly used by biologists and psychologists to accelerate neurological, pharmacological, and behavioral studies.Rodent behavioral analysis is often used to assess the effects of pharmaceuticals, implanted devices, or surgical procedures in preclinical research. The development of image analysis tools has enabled researchers to quantitatively assess various rodent behaviors quickly and objectively 1,2 . However, most automated scoring programs track patterns in spatial locomotor exploration and neglect ethological behaviors, such as head dipping and stretch-attend posture (SAP) 1 . Currently, there is no accurate tracking and scoring software that can directly detect SAP 3 . SAP, which is generally associated with anxiety, occurs when the rodent lowers its back, elongates its body, and is either standing still or moving forward very slowly 4 . SAP is a naturally occurring behavior found in rodents, such as mice, etc. that can be reliably intensified by certain experimental paradigms, such as placing the rodent in an open-field test 4,5 . In mice, the SAP behavior occurs when the mouse is undergoing risk-assessment specifically due to an internal exploratory-anxiety conflict. It can also occur under fearful risk-assessment where SAP would be an ambivalent element reflecting an approach-avoidance tendency 4,6 . When SAP is present during a passive avoidance situation, mice approach or avoid the object at nearly equal rates, which indicates they are undergoing risk-assessment during an approach-avoidance conflict 5,6 . SAP is a good identifier for conflict behavior in mice and can be used to evaluate the effects of drugs at reducing these internal conflicts 7 . During exploratory-anxiety conflict situations, SAP can be used as a valid measure of anxiety as anxiolytic drugs have successfully reduced SAP 5,7-9 .SAP has been evaluated in elevated plus maze (EPM) 10 , open field (OF) 11 , rat exposure test 12 , and canopy stretch attend posture test 8 . Increased SAP behavior of rodents near the entrance of the open arms in EPM and along the border of the canopy in the canopy stretch attend po...

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“…Interestingly, the complex treatment in selectively bred animals resulted in an altered motor phenotype with decreased rearing and walking activity, accompanied by increased exploratory and grooming activities. The enhanced grooming behavior can indicate anxiety, and might present a useful strategy to investigate stress-related responses in animal models of neuropsychiatric disorders [209][210][211]. To clarify these results regarding the different aspects of motor behavior, further investigation of motor behavior is necessary in these animals.…”

Section: Motor Activitymentioning

confidence: 99%

Development and characterization of chronic animal models of schizophrenia

Petrovszki¹

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Experimental Models of Anxiety for Drug Discovery and Brain Research

Cited by 46 publications

References 38 publications

Rhythmic brain stimulation reduces anxiety-related behavior in a mouse model based on meditation training

Rhythmic brain stimulation reduces anxiety-related behavior in a mouse model based on meditation training

MATSAP: An Automated Analysis of Stretch-Attend Posture in Rodent Behavioral Experiments

Development and characterization of chronic animal models of schizophrenia

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