Psychostimulant Addiction and Nutrient-Sensing Neurons: Genetic Targeting to Parse Neuro Pathways

Led by Dr. Ken WakabayashiUniversity of Nebraska-Lincoln

Study Overview:

Cocaine and methamphetamine (meth) use disorders may involve nutrient-sensing circuits including melanin concentrating hormone (MCH) neurons in brain areas such as the lateral hypothalamus (LH). This project will determine how cocaine or meth experience affects MCH neuronal activity and LH glucose levels, highlighting a possible mechanism, and verify the role of MCH neurons in regulating addiction-like behavior.

Specific Aims:

(Aim 1): To determine the changes in MCH neuronal activity after psychostimulant experience and link it to extracellular glucose levels in vivo.

(Aim 2): Experiments will determine the functional role of MCH neurons in regulating long access and intermittent access cocaine or methamphetamine self-administration, two approaches that produce addiction-like behavior in rats.

Study Sample Population:

N=576 (576 rats total, 192 per year over three years).

Unique Study Procedures:

Genetically encoded calcium indicators (GECIs), in vivo fiber photometry and glucose biosensors, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs).

Long-Term Goals:

Ultimately, this research contributes to the basic biological mechanisms underlying cocaine and meth addiction and is an important part of developing more effective therapeutic interventions at both the national and local level.

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Ken Wakabayashi

Dr. Ken WakabayashiProject Director

Dr. Wakabayashi received his Ph.D. in neuroscience from the University of Michigan, Ann Arbor. He was a post-doc at the National Institute on Drug Abuse (NIDA) from 2010-2015 and at the University at Buffalo (SUNY) Clinical Research Institute on Addiction from 2015-2019. His work is focused on understanding the fundamental processes in the brain underpinning reward-seeking behavior, and how these systems can become hijacked by drugs of abuse in addiction and alcoholism.

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Project Leaders

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Shilpa Buch

Shilpa BuchMentor

As Professor and Vice Chair of the Department of Pharmacology and Experimental Neuroscience at the University of Nebraska Medical Center (UNMC) and as Director of UNMC’s Nebraska Center for Substance Abuse Research, Dr. Shilpa Buch advises the RDAR Center on emerging opportunities in biomedical research on addiction. She also serves as the main point of contact for the Center at UNMC, helping to identify new hires and early career scholars that could participate in RDAR’s programs as Project Leaders or Pilot Project investigators.

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Rick Bevins

Rick BevinsMentor

Dr. Bevins leads the RDAR Center with 20 years of research experience ranging from psychology to immunology, cognition to neurochemistry, methamphetamine and tobacco addiction, vaccine development and medication testing, as well as robust translational science and model development. Previously, he has served as Associate Director for the Center from its inception in 2019. As Director, he now works closely with Center Coordinator Crawford and Associate Director Buch to guide its development. As the main point of contact with other regional COBRE/INBRE centers, Bevins interacts with other institutions working on issues of health and wellness in the Great Plains and across the United States.

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