Anxiety and Depression
Anxiety and depression encompass a wide spectrum of disease states. Anxiety disorders include Generalized Anxiety Disorder (GAD), panic disorder, obsessive compulsive disorder, and Post Traumatic Stress Disorder (PTSD). Depression is the most prevalent psychiatric disorder characterized by a state of sadness, despair, discouragement, and hopelessness. Other symptoms may include apathy, withdrawal from social contact, an inability to experience pleasure, changes in appetite and sleep patterns, low energy levels, difficulty concentrating, and thoughts of suicide.
PowerPoint Presentation outlining additional validation data for Depression Key aspects of these disease states can be recapitulated in rodents in the following tests.
- Light/Dark Choice
The light-dark choice test is a standard anxiety test which measures the effect of pharmacologic agents on the animal’s tendency to remain in dark vs. light areas. Anxiolytics increase the time spent in a well illuminated area.
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Elevated Plus Maze
The elevated plus maze is widely used as an anxiety paradigm and is based on unconditioned responses of mice to a potentially dangerous environment. A combination of maze height, luminosity and open space is assumed to induce fear or anxiety, the degree of which is assessed by measuring the amount of time mice spend in various areas of the maze.

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- Stress-Induced Hyperthermia
Body temperature and emotional state are closely related in humans, and stress-induced hyperthermia in mice is considered to have predictive validity for certain human anxiety/stress disorders. This test assesses the effect of anxiolytics on stress-induced hyperthermia and measures the intrinsic effects of these drugs on core body temperature.

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- Fear Potentiated Startle in Rats
An auditory startle response can be augmented by presenting the startle-eliciting noise with a stimulus that has previously been paired with an electric shock. The augmented startle response is called the fear-potentiated startle (FPS) and is considered a measure of fear. Clinically effective anxiolytics including benzodiazepines decrease or block the FPS.
- Open Field
The open field test is used to study behavioral responses in mice that are placed in a novel and bright arena. Mice tend to avoid brightly illuminated areas. The test also measures a range of anxiety-induced, locomotor activity and exploratory behaviors.
- Ultrasonic Vocalization in Guinea Pig Pups
This test measures anxiety and activity induced through isolation from the mother and siblings. The endpoint measures, motor responses and ultrasonic vocalizations of the isolated pups are very sensitive to a variety of pharmacological agents.

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- Marble Burying
Marble burying is used as a model for both anxiety and obsessive compulsive disorder. Mice are placed individually in clean mouse cages containing 5-cm of hard wood bedding. Marbles are placed in each cage in evenly spaced rows. Mice pretreated with anxiolytic agents show less marble burying compared to the control mice.

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- Conditioned Defensive Burying
The conditioned defensive burying test is used to study both anxiolytic and antidepressant drugs, and may also be used to study memory. It measures the effects of an aversive stimulus (mild shock when animal touches a probe) on behavior.
- Novelty Suppressed Feeding
This test assesses stress-induced anxiety by measuring the latency of an animal to approach and eat a familiar food in an aversive environment. The test is very sensitive to chronic antidepressant treatment but insensitive to acute treatment. Novelty suppressed feeding is therefore one of the few behavioral tests differentially sensitive to chronic vs. acute responses of antidepressants

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- Differential Reinforcement of Low Rate of Responding (DRL)
DRL is an operant test used to measure motor impulsivity involving behavioral suppression and withholding of a response for a period or time. While DRL is sensitive to the effects of certain cognitive enhancers, the test also has predictive validity for antidepressant drugs.
- Forced Swim in Mice and Rats
When rats or mice are forced to swim in a deep cylinder with tepid water they become nearly immobile and cease trying to escape. This characteristic immobile posture is thought to reflect a depressive-like state and is readily influenced by a wide variety of antidepressants.
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- Tail Suspension
When mice are suspended by their tails, they become motionless which, as with the forced swim test, is thought to reflect a depressive-like state. This immobility is reduced by a large variety of clinically active typical and atypical antidepressants.

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- Olfactory Bulbectomy in Rats
Removal of the olfactory bulb in rats is associated with variety of behavioral abnormalities including hyperactivity in the “open field” test. Chronic administration of antidepressants reduces the olfactory bulbectomy-induced hyperactivity in rats.

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