NIH Awards Scientists $2.3 Million Grant to Develop New Treatments for Drug Addiction

A pair of scientists on the Florida campus of The Scripps Research Institute has been awarded a $2.3 million grant by the National Institutes of Health (NIH) to conduct research relevant to developing new treatments for drug addiction.

Patricia McDonald, an associate scientific director in the Translational Research Institute at Scripps Florida and an assistant professor in the Department of Molecular Therapeutics, and Theodore Kamenecka, an associate scientific director in the Translational Research Institute, are co-principal investigators for the five-year project funded by the NIH's National Institute on Drug Abuse (NIDA).

The research will focus on indentifying compounds that affect the Neurotensin receptor (NTSR1), a receptor that appears to play a significant role in drug addiction because of its ability to alter levels of the neurotransmitter dopamine in the brain.

"Despite almost three decades of work by the pharmaceutical industry and other researchers, there are still few compounds known to act on NTSR1," said McDonald. "This new funding will help us thoroughly explore the interactions between the receptor and its signaling pathways and its impact on dopamine, which helps drive addiction and relapse."

The neurotransmitter dopamine is released when addictive drugs stimulate a reward circuit in the brain. Drug-induced changes in the reward circuit then reinforce the link between the pleasurable experience and the drug, increasing the tendency towards addiction. Blocking the surge of dopamine could protect the brain from these addictive changes, while substantially reducing the risk of relapse.

Kamenecka noted, "Our grant was something special in the sense that the NIH was looking for something very specific – new ways to accelerate the search for potential treatments of central nervous system disorders, which is what we expect to deliver. It also provides a good opportunity for Patsy's and my laboratories to collaborate on an important therapeutic area – drug addiction is an area with a lot of unmet medical needs."

The scientists said they expect to use a multiple test or assay approach to identify compounds that act on NTSR1, a method both believe will be an improvement over the current single assay approach typically used in the pharmaceutical industry.

"We want to avoid missing any potentially valuable compounds," McDonald noted, "so we plan to cast as wide a net as possible to capture compounds that modulate the receptor through different mechanisms."

If the team identifies compounds of interest, the scientists plan to determine their "functional fingerprint," then work with addiction experts at Scripps Florida, such as Associate Professor Paul Kenny, to help validate the compounds as potential therapeutics for addiction. Their search may ultimately move beyond addiction, however, since NTSR1 and related receptors such as NTSR2 and NTSR3 are also involved in diseases such as Alzheimer's, Parkinson's, and even some cancers.

Send comments to: mikaono[at]scripps.edu

Scripps Florida's Patricia McDonald (top) and Theodore Kamenecka plan to cast a wide net to capture compounds that act on a receptor that appears to play a significant role in drug addiction. (Photos by Randy Smith (top) and James McEntee.)