Opioid treatment has been shown to have profound neuroimmune effects. Morphine causes generalized suppression of immune function leading to an increased incidence of opportunistic disease and infection and has been shown to alter levels of receptors, such as the NMDA receptor, leading to neurochemical changes within the brain. These neurochemical changes have been implicated in the development of tolerance and dependence to the analgesic, immuno-suppressive and addictive properties of opioids. While most neuroimmune studies have traditionally used passive treatment paradigms (injection or subcutaneous pellet), addiction studies of opioids generally utilize the self-administration paradigm where animals must work to receive drug and are therefore """"""""contingently-dosed."""""""" Although clinically relevant to a drug-abusing population, little work has been done to study the neuroimmune effects of self-administered opioids. To test the hypothesis that neuroimmune changes in animals passively administered opioids may differ during self-administration, the experiments proposed here will look at the effects of opioids in animals that are self- administering morphine and """"""""yoked"""""""" animals that receive morphine passively.
The specific aims of this proposal are to: 1) characterize immune changes by looking at cellular and humoral immune function, 2) measure corticosterone levels to determine hypothalamic-pituitary axis response, 3) determine changes in NMDA receptor subunit regulation and, 4) examine neurochemical changes by analyzing NMDA receptor-mediated dopamine release in relevant brain regions during contingent and non-contingent opioid treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31DA014426-01
Application #
6400323
Study Section
Special Emphasis Panel (ZRG1-GRM (20))
Program Officer
Hoffman, Allison
Project Start
2001-07-01
Project End
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
1
Fiscal Year
2001
Total Cost
$22,155
Indirect Cost
Name
Georgetown University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
Ballard, Kimberly A; Pellegrino, Trisha C; Alonzo, Norma C et al. (2006) Enhanced immune sensitivity to stress following chronic morphine exposure. J Neuroimmune Pharmacol 1:106-15
Alonzo, Norma C; Bayer, Barbara M (2002) Opioids, immunology, and host defenses of intravenous drug abusers. Infect Dis Clin North Am 16:553-69