Opioid abuse has undergone a resurgence in the last decade. Although many opioids can be swallowed, snorted, or smoked, injectable opioids (especially heroin) have figured most prominently in the HIV epidemic. Injection drug users and their partners and children currently account for 36% of cumulative AIDS cases in the U.S. To improve access to pharmacotherapy for opioid dependence, the federal Drug Addiction Treatment Act (2000) and the Food and Drug Administration (2002) approved buprenrophine for opioid addiction treatment. Buprenorphine is a partial agonist at the mu opioid receptor and an antagonist at the kappa opioid receptor. Because mu receptor activation has been shown to stimulate HIV expression in monocytic cells, while kappa receptor activation inhibits HIV expression in these cells, buprenorphine's activity at the kappa receptor may be attenuate HIV expression. This may in turn be important for disrupting the synergistic processes that HIV infection and opioid dependence play in advancing neurocognitive decline. In this proposal, we will test the overarching hypothesis that pharmacological antagonism of kappa opioid receptors, such as that obtained with buprenorphine, may improve neurocognitive function in opioiddependent drug users with HIV infection. We will examine the impact of buprenorphine on changes in neurocognitive (NC) function among opioid-dependent persons with and without HIV-infection, and create a plasma bank to identify biomarkers of neurocognitive changes associated with buprenorphine initiation and maintenance. A cohort of 40 HIV-infected opioid-dependent persons and 40 HIV-seronegative opioiddependent perons newly initiated on buprenorphine will be recruited and serial NC testing will be adminstered and serial blood samples obtained. We will conduct a proteomic analysis to identify biomarkers in platelet poor plasma of buprenorphine administration and neurocognitive outcome in fifteen HIV-infected opioid-dependent persons, using a pre/post design.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory Grants (P20)
Project #
5P20DA026149-03
Application #
8234090
Study Section
Special Emphasis Panel (ZDA1)
Project Start
Project End
2012-02-29
Budget Start
2011-03-01
Budget End
2012-02-29
Support Year
3
Fiscal Year
2011
Total Cost
$165,637
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
Nika, Heinz; Angeletti, Ruth Hogue; Hawke, David H (2016) Phosphopeptide Enrichment by Covalent Chromatography After Solid Phase Derivatization of Protein Digests on Reversed Phase Supports. Methods Mol Biol 1355:31-50
Arias, Franchesca; Arnsten, Julia H; Cunningham, Chinazo O et al. (2016) Neurocognitive, psychiatric, and substance use characteristics in opioid dependent adults. Addict Behav 60:137-43
Carvallo, Loreto; Lopez, Lillie; Che, Fa-Yun et al. (2015) Buprenorphine decreases the CCL2-mediated chemotactic response of monocytes. J Immunol 194:3246-58
Nika, Heinz; Angeletti, Ruth Hogue; Hawke, David H (2014) N-terminal protein characterization by mass spectrometry using combined microscale liquid and solid-phase derivatization. J Biomol Tech 25:77-86
Nika, Heinz; Hawke, David H; Angeletti, Ruth Hogue (2014) N-terminal protein characterization by mass spectrometry after cyanogen bromide cleavage using combined microscale liquid- and solid-phase derivatization. J Biomol Tech 25:19-30
Nika, Heinz; Hawke, David H; Angeletti, Ruth Hogue (2014) C-terminal protein characterization by mass spectrometry: isolation of C-terminal fragments from cyanogen bromide-cleaved protein. J Biomol Tech 25:1-18
Nika, Heinz; Nieves, Edward; Hawke, David H et al. (2013) Optimization of the ?-elimination/michael addition chemistry on reversed-phase supports for mass spectrometry analysis of O-linked protein modifications. J Biomol Tech 24:132-53
Nika, Heinz; Nieves, Edward; Hawke, David H et al. (2013) C-terminal protein characterization by mass spectrometry using combined micro scale liquid and solid-phase derivatization. J Biomol Tech 24:17-31
Berezniuk, Iryna; Lyons, Peter J; Sironi, Juan J et al. (2013) Cytosolic carboxypeptidase 5 removes ?- and ?-linked glutamates from tubulin. J Biol Chem 288:30445-53
Fleitz, Antoine; Nieves, Edward; Madrid-Aliste, Carlos et al. (2013) Enhanced detection of multiply phosphorylated peptides and identification of their sites of modification. Anal Chem 85:8566-76

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