CNS / Behavior
Anxiety & Depression
Elevated Plus Maze for Anxiety
Anxiety is an element in many affective disorders. The elevated plus maze assay assesses anxiety-like behavior in animals. The maze consists of two closed (with walls) and two open (no walls) arms. Untreated wild type mice tend to spend more time in the closed arms of the maze. An increase in the time spent in the open arms usually is interpreted as a decrease of anxiety-like behavior. The mice are placed in the center area of the elevated plus maze and allowed to explore the maze. Movements of the animals are monitored by a video camera connected to a computer. Software automatically determines the number of entries into each arm, the time spent in each arm and the time spent in the center of the maze.
Novel Environment-Induced Feeding Suppression for Anxiety
This paradigm is based on an observation that when animals are placed in a novel environment, the latency to consume a familiar palatable snack is markedly prolonged. These effects are blocked or attenuated by various pharmacological treatments known to alleviate anxiety in people. In this test, the mice are habituated to novel palatable food introduced for a short period of time in their home cages. On the day of the experiment, the mice are placed in a clean cage (new environment) and the food is introduced as before. The latency to consumption (eating) is recorded. This model is akin to the elevated plus maze test described above, in which there is a conflict between the drive to explore (and seek out new sourced of food) and the response inhibition imposed by the potential threat of the new environment.
Open Field for Locomotion and Anxiety
Hyperactivity and hypoactivity are symptoms of many neuropsychiatric disorders. In addition, many advanced behavioral assays are locomotion-dependent and cannot be performed on animals with severely impaired locomotor activity (LMA). Therefore LMA of genetically modified or pharmacologically treated mice is often assessed prior to advance testing to assess any effects of locomotion on the results of other behavioral assays. The reaction to a novel environment and anxiety parameters are also assessed in this assay. The percent path length and the time spent in the center of the arena are often used as measures of anxiety-like behavior in mice. Generally, mice avoid the center of the open field apparatus, the most exposed part of the arena. An increase in activity or time spent in the center of the open field is interpreted as decreased anxiety-like behavior. In our open field paradigm, the mouse movements are followed by a video-racking system in a square shaped apparatus during a one-hour period. The locomotor activity is determined in 5 min bins for the total path length, the percent path length, and the time in the center of the arena.
Tail Suspension Test for Depression
The tail suspension test is a model to study depression-like behavior in mice. Unlike many behavioral paradigms that were originally created for rats and later adopted for mice, this test was designed specifically for mice. In this test, the mice are suspended by their tails, and the duration of immobility and struggle episodes are measured by a force transducer connected to a computer. Immobility in this assay represents defeat or depression. Mice with longer lasting immobility are interpreted to have increased depression-like behavior.
General CNS / Behavior
Pentylenetetrazole- (PTZ-) Induced Seizures
Pentylenetetrazole-(PTZ-) induced seizures mimic seizure types seen in epilepsy and other diseases. PTZ is a non-competitive GABAA antagonist, which lowers neuronal inhibition. PTZ is administered via timed tail vein infusion to measure the threshold dose that causes three types of seizures: facial & forelimb clonus, running-bouncing clonus, and a tonic hind limb extensor seizure. The latency to each seizure is recorded, and the threshold dose (mg/kg) causing each type of seizure is calculated. An increased or decreased threshold dose in genetically modified or pharmacologically treated mice provides a quantitative measurement of the neuro-inhibitory or excitatory potential of the genetic mutation or the test compound.
Irwin Observational Battery
Gross examination of animals is often a useful first step to evaluate a potential pharmacological effect or an effect of a gene knockout. The Irwin observational battery systematically assesses animals in four major categories: physical characteristics, behavioral responses, neurological responses, and autonomic responses. The mice are observed by a trained operator, who assesses 48 individual endpoints to identify abnormalities and score the behavioral and physiological state of the mice.
Long Term Monitoring for Activity
Long term activity monitored continuously over a period of 72 hr in the comprehensive cage monitoring system (CCMS). Ambulatory and non-ambulatory horizontal activity, vertical activity (rearing events) and licking frequency are recorded. The activity data provides information on locomotor activity and habituation to a novel environment.
Feeding Behavior (Food Intake)
Effect of pharmacological treatment or genetic modification on feeding behavior is evaluated in fed and/or fasting mice. The feeding behavior is examined by determining the amount of food consumed over a span of 1-24 hr.
Micturition Behavior (Bladder Function)
Urinary Bladder Capacity and Function
This assay is designed to identify genetic targets or compounds that affect urinary bladder capacity in an effort to find new therapeutic targets for urinary urge incontinence. The bladder capacity and function assay utilizes a novel piece of equipment designed, built, and validated at Xenogen Biosciences, the Micturition Monitoring System (MMS). Following an intraperatoneal injection of saline, the mice are placed in the MMS chambers and all voiding events are monitored and recorded by a computer. The amount of urine per void, the voiding frequency, and the total amount of urine produced over a three hour period are determined. These endpoints are collectively utilized to assess the bladder function of mice.
Learning & Memory
Novel Object Recognition for Learning and Memory*
This test is used to assess working memory based on the inherent tendency of mice to explore novel objects more than familiar objects. This test can assess the effect of genetic manipulation and potential therapeutic compounds on acquisition, consolidation and retrieval of object recognition memory in one trial paradigm without use of positive or negative reinforcers. Mice are familiarized to a pair of objects followed by reintroduction of the animal to a second pair of objects, one of which is from the previously exposed pair and one is a novel object. The proportion of time spent by a mouse with the novel object as compared to the familiar object is used as measure of working memory
Accelerating Rotarod Assay for Motor Coordination and Learning
The accelerating rotarod test is a classic method to assess motor coordination, balance, and motor learning in mice. In this test, a mouse is placed on a rotating rod. The speed of rotation is gradually increased and the mouse’s ability to remain on the rotating rod is recorded. The parameter describing an animal’s ability is the time the animal is able to stay on the rotating rod combined with the speed of the rod at which the animal loses balance.
Motor Strength and Coordination
Inverted Grid Test for Motor Coordination*
This test is used to assess motor performance and strength. A mesh with standard grid size is used for this assay. The mesh is inverted after placement of mouse so that the mouse is upside down. The average forepaw step distance, percent wall time and percent forepaw faults are used to assess the motor performance.
Schizophrenia
Startle Amplitude and Pre-Pulse Inhibition for Schizophrenia and other Psychiatric Disorders
The startle and pre-pulse inhibition (PPI) assay is a model to assess sensory processing. PPI is elicited by presenting a lower decibel stimulus pre-pulse prior to a startling stimulus pulse. Normally, these pre-pulses will inhibit the startle response. A decrease in the percent PPI indicates a deficit in sensorimotor gating. Sensorimotor gating refers to processes by which organisms filter the input of environmental information and gate or adjust their behavior. Sensorimotor gating deficits are associated with several neuropsychiatric disorders, such as schizophrenia and obsessive-compulsive disorder, and are theorized to underlie cognitive disturbances in these disorders. This assay also measures startle sensitivity. Startle sensitivity to different audible pulses (0-120 dB) is measured on Day 1. On Day 2 pre-pulses at lower decibels precede some of the 120 dB pulses to measure PPI to the startle response.
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