Mentor: David Lin
Contact Information: Email: firstname.lastname@example.org; Phone: 607-253-4350
Sponsor: John’s Hopkins Center for Alternative to Animal Testing
Grant Number: AWE-2011-53
Title: Alleviating Human Induced Fear Response in Mice
Annual Direct Cost: $6,000
Project Period: 02/01/11-01/31/12
DESCRIPTION (provided by applicant): In the United States, as many as 30 million mice are used in biomedical research, testing, and education each year. Inbred laboratory rodents which have been isolated from predators for hundreds of generations still respond with a fear-like defensive behavior to cat and rat odors. In mice, the vomeronasal organ (VNO), a pheromone sensing component of the olfactory system, detects and processes predator odors that stimulate innate avoidance and fear assessment behaviors. To our knowledge, there has been no study regarding whether or not laboratory mice are innately afraid of humans. Our hypothesis is that laboratory mice have an innate fear of humans. In the animal facility where mice are cared for and used by humans, mice may live in a state of chronic emotional and physiological stress. If this is the case, suffering from fear and anxiety disorders would reduce welfare as well as confound research outcomes, decrease lifespan, and increase disease frequency and severity. We intend to improve animal welfare and refine the housing, handling, and experimental situations for laboratory mice.
The three objectives of this study are to (1) determine if mice have an innate fear of humans, (2) identify the human odor that elicits this fear, and (3) attempt to alleviate human induced fear in mice through non-invasive VNO exposure to fear-inducing odorants (habituation/ desensitization). First, a control mouse behavioral assay will be performed with known predator odors to elicit stereotypical fearful behaviors as described by Papes et al. (2010). An additional behavioral assay will then be used to evaluate commercially available human extracts’ propensity for eliciting innate fear responses in mice. After a fear-inducing human odor is isolated, habituation of neonatal mice and desensitization of adult mice will be attempted. Neonatal pups will be reared in an environment containing the human extract during their olfactory developmental period and naive adult mice will be exposed regularly to the human extract. Aversion, exploratory behavior, and attraction will be measured by the time spent in three arbitrarily assigned sections in a test cage. Statistical analysis of the data includes unpaired T tests and one-way ANOVA tests.
The anticipated outcomes of the study include the development of a non-invasive method to alleviate human-induced fear response in mice in a way that behavioral stress responses to common husbandry, such as capture, would be reduced. As a result, it would make mice more likely to cooperate than resist, requiring less invasive methods of restraint; thus directly improving their welfare. In addition, due to the reduced frequency of fear-related aggression in lab animals the safety of laboratory staff would improve. Lastly, variables associated with stress in mice would be reduced in biomedical research studies allowing for more accurate results during testing.