Psychology professor secures $2.59 million NIH grant to study the brain mechanisms of addiction

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A five-year, $2.59 million grant from the National Institutes of Health will allow a psychology professor at Binghamton University, State University of New York to study the mechanisms of addiction.

Binghamton University Associate Professor of Psychology, Anushri Karkhanis, along with Drexel University Associate Professor, Jessica, received a five-year $2.59 million grant from the National Institutes of Health for their project: “Mechanisms of Rostrocaudal Differences in the Effects of Concurrent Kappa-Opioid Receptors on Ethanol Drinking.”.

This project allows us to look at specific groups of neurons and how this particular receptor we’re studying modulates two different groups of neurons within a region of the brain. “

Anushri Karkhanis, Assistant Professor of Psychology, Binghamton University

Karkhanis first began researching the up-regulation of cumulative kappa opioid receptors during a postdoctoral fellowship at Wake Forest School of Medicine. Several laboratories in the United States, including hers, have shown that this receptor is modulated, which means that it increases its function after exposure to alcohol at different ages.

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Initially implicated in the treatment of addiction in animal models, recent studies have shown that opioid receptors have strong links to addiction in humans as well. For example, the drug naltrexone -; Most commonly used in the treatment of opioid overdoses, but also used to combat alcohol use disorder -; It blocks all opiate receptors in the brain.

The research project focuses on the rostral (anterior) and caudal (posterior) subregions of the nucleus accumbens cortex, which are involved in processing related to emotion and reinforcement. The hypothesis is that the two subregions of the mantle respond quite differently to pharmacological manipulation of kappa opioid receptors and alcohol use.

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The brain rewards behavior with dopamine, but the organic chemical doesn’t play the game alone; Every neurotransmitter system is involved to some degree. Karkhanis’ research targets the serotonin system, which is involved in mood, emotions, and stress, along with dopamine. Researchers believe that kappa opioid receptors modulate both neurotransmitter systems, but they don’t yet know the mechanism and whether each system is regulated differently.

In this five-year project, Karkhanis and Barson hope to answer that question, and learn how the modulation of neurotransmitter systems changes when an organism is exposed to alcohol. They will use mice in their research, and a combination of micro-injections and viral techniques to manipulate specific groups of neurons. Karkhanes’ lab also uses fast-scanning cyclic voltammetry, an electroanalytical method, to measure the release of neurotransmitters.

The idea behind the project got off the ground at a conference, where he invited Parson Karkhanis to speak in a panel discussion. In her talk, the latter touched on the rostro- and caudal differences in dopamine transmission following activation of kappa-opioid receptors. Next, they chatted over coffee about the data Parson was seeing in her lab after one of her students saw opposite effects after performing microinjections that activate kappa-opioid receptors along the caudal axis in the nucleus accumbens. Parson’s data worked well with the data produced by Kerkhanis.

“We literally drew an outline on a paper napkin, which is a kind of constant banter in science about how scientific ideas are conceived,” Karkhanis recalls.

In the long term, this research could improve treatment options for individuals with alcohol use disorder. While naltrexone is effective, it also carries multiple side effects and many patients do not pursue treatment. Research may discover ways to reduce the dose of naltrexone, or look for other medications that can target treatment.

“This grant actually gives my lab a chance to go in a very new direction like discovering serotonin; and the technology I use in my lab is not very common,” Karkhanes said. “It connects my lab to a very new area, and highlights the role of serotonin in alcohol use disorder.”

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