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
Research Transition Award (R00)
Project #
5R00AA020539-05
Application #
8901731
Study Section
Special Emphasis Panel (NSS)
Program Officer
Egli, Mark
Project Start
2013-09-05
Project End
2016-08-31
Budget Start
2015-09-01
Budget End
2016-08-31
Support Year
5
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Purdue University
Department
Type
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907
Alongkronrusmee, Doungkamol; Chiang, Terrance; van Rijn, Richard M (2018) Delta Opioid Pharmacology in Relation to Alcohol Behaviors. Handb Exp Pharmacol 247:199-225
Zeng, Lily; Alongkronrusmee, Doungkamol; van Rijn, Richard M (2017) An integrated perspective on diabetic, alcoholic, and drug-induced neuropathy, etiology, and treatment in the US. J Pain Res 10:219-228
Nie, Bin'en; Long, Teng; Ao, Haiyong et al. (2017) Covalent Immobilization of Enoxacin onto Titanium Implant Surfaces for Inhibiting Multiple Bacterial Species Infection and In Vivo Methicillin-Resistant Staphylococcus aureus Infection Prophylaxis. Antimicrob Agents Chemother 61:
Robins, Meridith T; DeFriel, Julia N; van Rijn, Richard M (2016) Adolescent intake of caffeinated energy drinks does not affect adult alcohol consumption in C57BL/6 and BALB/c mice. Alcohol 54:1-9
Robins, Meridith T; Lu, Julie; van Rijn, Richard M (2016) Unique Behavioral and Neurochemical Effects Induced by Repeated Adolescent Consumption of Caffeine-Mixed Alcohol in C57BL/6 Mice. PLoS One 11:e0158189
Yang, Sungchil; Ben-Shalom, Roy; Ahn, Misol et al. (2016) ?-Arrestin-Dependent Dopaminergic Regulation of Calcium Channel Activity in the Axon Initial Segment. Cell Rep 16:1518-1526
Chiang, T; Sansuk, K; van Rijn, R M (2016) ?-Arrestin 2 dependence of ? opioid receptor agonists is correlated with alcohol intake. Br J Pharmacol 173:332-43
Alongkronrusmee, Doungkamol; Chiang, Terrance; van Rijn, Richard M (2016) Involvement of delta opioid receptors in alcohol withdrawal-induced mechanical allodynia in male C57BL/6 mice. Drug Alcohol Depend 167:190-8