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

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
Office of The Director, National Institutes of Health (OD)
Type
Resource-Related Research Projects (R24)
Project #
8R24OD011180-15
Application #
8327722
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Watson, William T
Project Start
1996-09-30
Project End
2013-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
15
Fiscal Year
2012
Total Cost
$699,388
Indirect Cost
$173,687
Name
Harvard University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Vandeleest, J J; Capitanio, J P; Hamel, A et al. (2018) Social stability influences the association between adrenal responsiveness and hair cortisol concentrations in rhesus macaques. Psychoneuroendocrinology 100:164-171
Hamel, A F; Menard, M T; Novak, M A (2017) Fatty acid supplements improve hair coat condition in rhesus macaques. J Med Primatol 46:248-251
Dettmer, Amanda M; Wooddell, Lauren J; Rosenberg, Kendra L et al. (2017) Associations between early life experience, chronic HPA axis activity, and adult social rank in rhesus monkeys. Soc Neurosci 12:92-101
Grant, Kimberly S; Worlein, Julie M; Meyer, Jerrold S et al. (2017) A longitudinal study of hair cortisol concentrations in Macaca nemestrina mothers and infants. Am J Primatol 79:1-9
Novak, Melinda A; Menard, Mark T; El-Mallah, Saif N et al. (2017) Assessing significant (>30%) alopecia as a possible biomarker for stress in captive rhesus monkeys (Macaca mulatta). Am J Primatol 79:1-8
Stanwicks, Lauren L; Hamel, Amanda F; Novak, Melinda A (2017) Rhesus macaques (Macaca mulatta) displaying self-injurious behavior show more sleep disruption than controls. Appl Anim Behav Sci 197:62-67
Peterson, Emily J; Worlein, Julie M; Lee, Grace H et al. (2017) Rhesus macaques (Macaca mulatta) with self-injurious behavior show less behavioral anxiety during the human intruder test. Am J Primatol 79:1-8
Dettmer, Amanda M; Rosenberg, Kendra; Menard, Mark T et al. (2017) Differential relationships between chronic hormone profiles in pregnancy and maternal investment in rhesus monkey mothers with hair loss in the neonatal period. Am J Primatol 79:1-8
Coleman, Kristine; Novak, Melinda A (2017) Environmental Enrichment in the 21st Century. ILAR J 58:295-307
Hamel, Amanda F; Lutz, Corrine K; Coleman, Kristine et al. (2017) Responses to the Human Intruder Test are related to hair cortisol phenotype and sex in rhesus macaques (Macaca mulatta). Am J Primatol 79:1-10

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