Study implicates dopamine in food restriction, drug abuse

Finding offers clue to developing treatments for misuse of illicit drugs

SAN ANTONIO (Aug. 20, 2013) — Scientists today reported a possible basis for why food-restricted animals show increased susceptibility to drugs of abuse. This association has puzzled researchers since it was first observed more than three decades ago.

Senior author Michael Beckstead, Ph.D., from the School of Medicine at The University of Texas Health Science Center San Antonio, said the team found that dopamine neurons in a brain region called the substantia nigra fire bursts more than twice as frequently in chronically food-restricted mice. Cocaine significantly enhanced this firing only in mice that were fed less, the team also found.

“Dopamine neurons are part of what we consider the main reward pathway in the brain,” said Dr. Beckstead, assistant professor of physiology. “They play a strong role in motivated behavior. There is an overlapping process between natural rewards and drug rewards that we studied here.”

Charles France, Ph.D., professor of pharmacology in the School of Medicine, in 1979 was on the team that first reported the connection between food restriction and behavioral effects from drugs of abuse. He was not associated with the new research, which is in The Journal of Neuroscience.

“We’ve had no idea how this happens in the brain,” Dr. Beckstead said. “This study identifies dopamine neurons of the substantia nigra as a convergence point for the interaction between feeding state and the effects of drugs of abuse. Food restriction is changing the system.” The substantia nigra is a structure located in the midbrain.

No approved treatments exist for psychostimulant abuse – drugs such as cocaine, amphetamine and methamphetamine. “We first need to understand how adaptations in the brain contribute to drug use in order to better design drugs,” Dr. Beckstead said. “However this finding, by giving us a clue as to how we might ‘adjust the gain’ on the system, is a very important early step in the development of therapy.”

The study authors are from the UT Health Science Center, The University of Texas at San Antonio (UTSA) Neurosciences Institute and the University of the Incarnate Word in San Antonio. Partial funding is by the San Antonio Life Sciences Institute, a joint initiative of the Health Science Center, UTSA and The University of Texas System that received funding from the Texas Legislature in 2010.

This work was funded by the National Institutes of Health through K01 (DA21699) and R01 Awards (DA32701) to Dr. Michael Beckstead, and R01 Awards (MH79276 and DA30530) to Dr. Carlos Paladini. Additional funding was provided by a grant from the Research Enhancement Fund through the San Antonio Life Sciences Institute (to Drs. Beckstead and Paladini), and American Heart Association National Scientist Development Grant SDG4350066 (to Dr. Amanda Sharpe).


Food Restriction Increases Glutamate Receptor-Mediated Burst Firing of Dopamine Neurons
The Journal of Neuroscience, August 21, 2013 • 33(34):13861–13872
Sarah Y. Branch,1 R. Brandon Goertz,3 Amanda L. Sharpe,5 Janie Pierce,3 Sudip Roy,3 Daijin Ko,4 Carlos A. Paladini,3 and Michael J. Beckstead1,2
1 Department of Physiology, and 2 Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, Texas 78229, 3 UTSA Neurosciences Institute, and 4 Department of Management Science and Statistics, University of Texas at San Antonio, San Antonio, Texas 78249, and 5 Feik School of Pharmacy, University of the Incarnate Word, San Antonio, Texas 78209

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