Alcoholism and alcohol related illnesses put a large strain on society. While therapeutics are available, none are universally effective among the diverse population of treatment seeking individuals. My research is focused on elucidating the role of two delta opioid receptor subtypes (DOR1 and DOR2) in alcohol abuse disorders. Their ability to affect both ethanol consumption and anxiety make these DOR subtypes promising potential novel drug targets to treat alcoholism. So far I have discovered that the DOR subtypes have unique and sometimes opposing effects on ethanol consumption and anxiety. Moreover, I determined that the DOR1's pharmacology may result from an interaction of the DOR with the MOR forming a DOR-MOR heteromer. My research is designed to determine the mechanism behind the unique pharmacology of the DOR subtypes and exploit it to develop novel drugs that can treat alcohol abuse disorders better and with fewer side effects than the currently available medication. One integral part of my research is resolving how chronic ethanol exposure results in an increase in the number of functional DORs. Additionally, I have designed a unique method to identify drugs that selectively interact with receptor heteromers using a high throughput in vitro assay. I intend to further test compounds identified in this assay using mice models of alcoholism, determining their effects on ethanol intake, anxiety, reward and ethanol withdrawal. My ultimate goal is to validate a DOR-subtype as a new target for intervention in alcohol abuse and determine the properties of the most ideal DOR-subtype selective drug as a preclinical lead.

Public Health Relevance

Alcoholism and alcohol related illnesses put a large strain on society. While therapeutics are available, none are universally effective among the diverse population of treatment seeking individuals. This proposal sets out to investigate novel drug targets and identify new lead compounds to better treat alcoholism with reduced side effects.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Career Transition Award (K99)
Project #
5K99AA020539-02
Application #
8322858
Study Section
Health Services Research Review Subcommittee (AA)
Program Officer
Egli, Mark
Project Start
2011-08-20
Project End
2013-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
2
Fiscal Year
2012
Total Cost
$88,419
Indirect Cost
$6,550
Name
Ernest Gallo Clinic and Research Center
Department
Type
DUNS #
173995366
City
Emeryville
State
CA
Country
United States
Zip Code
94608
van Rijn, Richard M; Harvey, Jessica H; Brissett, Daniela I et al. (2013) Novel screening assay for the selective detection of G-protein-coupled receptor heteromer signaling. J Pharmacol Exp Ther 344:179-88
Milan-Lobo, Laura; Enquist, Johan; van Rijn, Richard M et al. (2013) Anti-analgesic effect of the mu/delta opioid receptor heteromer revealed by ligand-biased antagonism. PLoS One 8:e58362
van Rijn, Richard M; Brissett, Daniela I; Whistler, Jennifer L (2012) Distinctive modulation of ethanol place preference by delta opioid receptor-selective agonists. Drug Alcohol Depend 122:156-9