Abuse liability and anti-addiction potential of the atypical ? opioid receptor agonist IBNtxA Opioid drugs are crucial medications to treat acute and chronic pain. However, they are commonly abused and therefore spur wide societal costs. Thus there is a need to develop new analgesics with reduced addiction liability and new treatments for opioid addiction. IBNtxA, a novel opioid drug that is believed to activate selected splice variants of the ? opioid receptor (MOR), is reported to have reduced side effect profiles compared to current opioid analgesics. In this proposal, we will evaluate the abuse liability and subjective properties of IBNtxA using two mouse models: conditioned place preference (CPP) and drug discrimination (DD). IBNtxA will be tested for its ability to alter morphine-mediated CPP and reinstatement of morphine CPP. These experiments will measure the subjective rewarding properties of IBNtxA, its abuse liability, and its potential as a treatment for opioid addiction. DD tests, comparing IBNtxA against classical opioid agonists, will determine whether IBNtxA produces morphine- like behavioral responses or whether its effects are distinct from current opioid ligands, representing a new biological target for medications development. These studies will provide a foundation for future studies with IBNtxA and structural analogues to determine the molecular mechanisms underlying IBNtxA?s more favorable side effect profile and the role of MOR splice variant signaling in the development and treatment of opioid addiction.

Public Health Relevance

Opioid drugs are crucial medications in treating pain but are also highly addictive. Thus there is a need to develop new analgesics with reduced addiction liability as well as new treatments for opioid addiction. IBNtxA is a new opioid drug that is reported to have reduced side effects than morphine, including reduced abuse liability. This proposal will evaluate the subjective effects of IBNtxA, the ability of IBNtxA to alter addiction-like behavior of morphine, and explore the potential use of IBNtxA as a treatment for opioid addiction. These studies will aid in the development of new treatments for pain and opioid addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Small Research Grants (R03)
Project #
1R03DA041560-01A1
Application #
9317755
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Rapaka, Rao
Project Start
2017-04-01
Project End
2019-03-31
Budget Start
2017-04-01
Budget End
2019-03-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Rowan University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
139203145
City
Glassboro
State
NJ
Country
United States
Zip Code
08028