Between 2010 and 2015, the combined overdose deaths from cocaine and psychostimulants with abuse potential—a drug category that includes methamphetamine, Adderall and Ritalin—equaled the number of overdose deaths from heroin.

West Virginia University doctoral candidate Joshua Gross is investigating how a particular protein influences the brain’s response to such drugs. Gross is conducting his research in collaboration with his two mentors: David Siderovski, Chair of WVU’s Physiology, Pharmacology, and Neuroscience Department, and Vincent Setola, Director of WVU’s Laboratory of Neuroscience and Genetics of Substance Abuse.

The National Institute of Drug Abuse, a division of the National Institutes of Health, awarded Gross a $132,132 fellowship for a three-year study into the role this protein—Regulator of G protein Signaling-12 (RGS12)—plays in triggering and sustaining addiction. His work is relevant to developing therapeutic treatments that target the protein at issue and help manage, or even prevent, psychostimulant addictions.

Gross’ research suggests that when drug users lack this protein, psychostimulants may not amp them up as much as users who have the protein intact. He also found that, without the protein, the brain gets more efficient at whisking away dopamine, a feel-good chemical that makes experiences seem rewarding and motivates us to seek them out in the future.

Less dopamine circulating in the brain leads to less euphoria and a smaller high from psychostimulants.

According to Gross, who is part of the WVU School of Medicine’s cellular and integrative physiologyprogram, addiction can’t happen without dopamine because nearly all psychostimulant drugs act on dopamine.

“To understand how the addictive process works is really important,” Gross said. “Just as somebody may hurt their back working construction, get prescribed OxyContin, and scale to heroin, the same thing could feasibly happen with drugs like Adderall. We’re prescribing them more and more to children, who are still undergoing neural development. Do they cause permanent changes? If so, how is that working?”

Gross’ most recent findings on the protein RGS12 are featured in the Journal of Psychopharmacology, which publishes research articles on the basic scientific and clinical aspects of how drugs affect mood, thought and behavior.

“Because the heroin epidemic is escalating at an unprecedented rate, it overshadows what’s happening in the background—things like methamphetamine and cocaine abuse,” Gross said. “But it’s still very much an issue, and it’s not going away.”

“We are proud of Josh’s accomplishments to date on a pressing West Virginia public health crisis, as well as the recent vote of confidence from NIDA on his potential to contribute meaningful insights into novel targets for developing anti-addiction therapies,” Siderovski said.

Research reported in this publication was supported by the National Institute of Drug Abuse of the National Institutes of Health under Award Number 1F31DA043331-01A1.  The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Joshua Gross’s publication appears in the “Journal of Psychopharmacology”: Gross et al., “Regulator of G protein signaling-12 modulates the dopamine transporter in ventral striatum and locomotor responses to psychostimulants,” “Journal of Psychopharmacology,” January 24, 2018. doi: 10.1177/0269881117742100.

(From Tara Scatterday for WVU Today. Photo courtesy of WVU Photo).