This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Two mutually exclusive hypotheses have emerged in humans implicating a role of the endogenous opioid (EO) system in (SIB). The pain hypothesis proposes that elevated EOs result in hypoalgesia leading to SIB as a form of self stimulation. In contrast, the self-administration hypothesis proposes that individuals engage in SIB to elevate EOs and relieve negative emotions. Importantly, we have shown that the EO system may be altered in monkeys with SIB. SIB monkeys preferentially directed biting to acupressure points (Marinus et al. 2000), which is thought to involve release of EOs in humans (Ulett et al. 1998). We have also reported reduced levels of plasma beta-endorphin (Tiefenbacher et al. 2003a) and CSF met-enkephalin (Tiefenbacher et al. 2003b) in monkeys with SIB. These findings suggest that SIB in our monkeys may be best explained by the self-administration hypothesis which serves to increase beta-endorphin levels. Based on findings in enkephalin and dynorphin knockout mice, that brain opioid receptors are up-regulated (Brady et al. 1999;Clarke et al. 2003), we hypothesized that mu-opioid receptors (MOR) are up-regulated in the brains of monkeys with SIB, increasing the positive effects of beta-endorphin release after biting.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000168-50
Application #
8358019
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
50
Fiscal Year
2011
Total Cost
$53,995
Indirect Cost
Name
Harvard University
Department
Veterinary Sciences
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Isakova, Irina A; Baker, Kate C; Dufour, Jason et al. (2016) Mesenchymal Stem Cells Yield Transient Improvements in Motor Function in an Infant Rhesus Macaque With Severe Early-Onset Krabbe Disease. Stem Cells Transl Med :
Williams, Kenneth; Lackner, Andrew; Mallard, Jaclyn (2016) Non-human primate models of SIV infection and CNS neuropathology. Curr Opin Virol 19:92-8
Kannanganat, Sunil; Wyatt, Linda S; Gangadhara, Sailaja et al. (2016) High Doses of GM-CSF Inhibit Antibody Responses in Rectal Secretions and Diminish Modified Vaccinia Ankara/Simian Immunodeficiency Virus Vaccine Protection in TRIM5α-Restrictive Macaques. J Immunol 197:3586-3596
Fischer, Bradford D; Platt, Donna M; Rallapalli, Sundari K et al. (2016) Antagonism of triazolam self-administration in rhesus monkeys responding under a progressive-ratio schedule: In vivo apparent pA2 analysis. Drug Alcohol Depend 158:22-9
Yasuda, Koji; Oh, Keunyoung; Ren, Boyu et al. (2015) Biogeography of the intestinal mucosal and lumenal microbiome in the rhesus macaque. Cell Host Microbe 17:385-91
Walker, Joshua A; Beck, Graham A; Campbell, Jennifer H et al. (2015) Anti-α4 Integrin Antibody Blocks Monocyte/Macrophage Traffic to the Heart and Decreases Cardiac Pathology in a SIV Infection Model of AIDS. J Am Heart Assoc 4:
Adnan, Sama; Colantonio, Arnaud D; Yu, Yi et al. (2015) CD8 T cell response maturation defined by anentropic specificity and repertoire depth correlates with SIVΔnef-induced protection. PLoS Pathog 11:e1004633
Gardner, Matthew R; Kattenhorn, Lisa M; Kondur, Hema R et al. (2015) AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges. Nature 519:87-91
Wang, Zichun; Metcalf, Benjamin; Kasheta, Melissa et al. (2015) Characterization of MHC class I alleles in sooty mangabeys as a tool for evaluating cellular immunity in natural hosts of SIV infection. Immunogenetics 67:447-61
Hallett, Penelope J; Deleidi, Michela; Astradsson, Arnar et al. (2015) Successful function of autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson's disease. Cell Stem Cell 16:269-74

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