The presence of severely abnormal behavior, such as self-injurious behavior (SIB) in laboratory housed primates compromises the quality of the animal research resource and adversely impacts research. In rhesus monkeys, SIB consists of intense, self-directed biting that can result in serious wounds requiring veterinary treatment. Based on findings from our laboratory and others, we have developed a model proposing that SIB arises from adverse life events, is maintained by dysregulation of several neurochemical and physiological systems, and functions to reduce anxiety. Unfortunately, SIB is resistant to treatment, alleviated neither by environmental enrichment nor changes in cage size. Pharmacological treatments have shown effectiveness in reducing SIB;however, relapse is common post-treatment, and long-term maintenance on drugs is undesirable for research purposes. The long-term goal of this project is to decrease the prevalence of SIB in captive primates by (1) preventing the onset of SIB through identification of key risk factors, and (2) developing novel treatments for this disorder that are cost-effective and produce long-lasting benefit. In furtherance of this goal, the proposed project will test the hypothesis that stress exposure and anxious behavior are precipitating factors in the development of SIB. To determine the generality of this hypothesis, factors contributing to SIB onset will be studied at 4 national primate research centers. To reduce the incidence of SIB in animals that have already developed this disorder, we will test a novel pharmacotherapeutic approach involving administration of the opioid receptor antagonist naltrexone. Short- term treatment with naltrexone has been shown to yield long-term decrements in SIB in many human patients, but this compound has not yet been tested on non-human primates. Finally, hair plucking (another type of SIB) and more generally hair loss have come under increased scrutiny from federal regulators. Consequently, we have enlarged the scope of this project to include hair loss, and we will test the hypothesis that hair loss in captive primates can result from several different factors, including hair plucking, stress and anxiety, and atopic dermatitis.

Public Health Relevance

(provided by applicant): This research is designed to improve the quality of the research resource. Rhesus monkeys are crucial in the development of models for many human diseases. The goal of this project is to determine the factors that contribute to the development of severely abnormal behavior in rhesus monkeys and to identify strategies for prevention and treatment.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Resource-Related Research Projects (R24)
Project #
2R24RR011122-14A1
Application #
8150168
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Watson, William T
Project Start
1996-09-30
Project End
2015-06-30
Budget Start
2011-09-03
Budget End
2012-06-30
Support Year
14
Fiscal Year
2011
Total Cost
$796,933
Indirect Cost
Name
Harvard University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Kelly, Brian; Maguire-Herring, Vanessa; Rose, Christian M et al. (2014) Short-term testosterone manipulations do not affect cognition or motor function but differentially modulate emotions in young and older male rhesus monkeys. Horm Behav 66:731-42
Simpson, Elizabeth A; Sclafani, Valentina; Paukner, Annika et al. (2014) Inhaled oxytocin increases positive social behaviors in newborn macaques. Proc Natl Acad Sci U S A 111:6922-7
Dettmer, A M; Novak, M A; Meyer, J S et al. (2014) Population density-dependent hair cortisol concentrations in rhesus monkeys (Macaca mulatta). Psychoneuroendocrinology 42:59-67
Meyer, Jerrold; Novak, Melinda; Hamel, Amanda et al. (2014) Extraction and analysis of cortisol from human and monkey hair. J Vis Exp :e50882
Novak, Melinda A; Hamel, Amanda F; Kelly, Brian J et al. (2013) Stress, the HPA axis, and nonhuman primate well-being: A review. Appl Anim Behav Sci 143:135-149
Meyer, Jerrold S; Novak, Melinda A (2012) Minireview: Hair cortisol: a novel biomarker of hypothalamic-pituitary-adrenocortical activity. Endocrinology 153:4120-7
Bechshoft, T O; Sonne, C; Dietz, R et al. (2012) Associations between complex OHC mixtures and thyroid and cortisol hormone levels in East Greenland polar bears. Environ Res 116:26-35
Dettmer, Amanda M; Novak, Melinda A; Suomi, Stephen J et al. (2012) Physiological and behavioral adaptation to relocation stress in differentially reared rhesus monkeys: hair cortisol as a biomarker for anxiety-related responses. Psychoneuroendocrinology 37:191-9
Bechshoft, T O; Riget, F F; Sonne, C et al. (2012) Measuring environmental stress in East Greenland polar bears, 1892-1927 and 1988-2009: what does hair cortisol tell us? Environ Int 45:15-21
Bechshoft, T O; Sonne, C; Dietz, R et al. (2011) Cortisol levels in hair of East Greenland polar bears. Sci Total Environ 409:831-4

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