The Intramural Research Program of the National Institute on Drug Abuse

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    The IRP is served by the best and brightest in the scientific community. Find out more about the scientists striving to solve the puzzles of drug addiction and its effects on the human brain.

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    The research of the Intramural Research Program is supported at the molecular, genetic, cellular, animal, and clinical levels and is conceptually integrated, highly innovative, and focused on major problems in the field of drug addiction research.

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    Intramural Research Program (IRP) of the National Institute on Drug Abuse is dedicated to innovative research on basic mechanisms that underlie drug abuse and dependence, and to develop new methods for the treatment of drug abuse and dependence.

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Li-Ming Hsu
Hot off the Press!

Constituents and functional implications of the rat default mode network

Proc Natl Acad Sci U.S.A. 2016 Aug 2;113(31):E4541-7. Epub 2016 Jul 20.

Li-Ming Hsu, Xia Liang, Hong Gu, Julia K. Brynildsen, Jennifer A. Stark, Jessica A. Ash, Ching-Po Lin, Hanbing Lu, Peter R. Rapp, Elliot A. Stein, and Yihong Yang

The default mode network (DMN) has been suggested to support a variety of self-referential functions in humans and has been fractionated into subsystems based on distinct responses to cognitive tasks and functional connectivity architecture. Such subsystems are thought to reflect functional hierarchy and segregation within the network. Because preclinical models can inform translational studies of neuropsychiatric disorders, partitioning of the DMN in nonhuman species, which has previously not been reported, may inform both physiology and pathophysiology of the human DMN....

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Dr. Geoffrey Schoenbaum.
Hot off the Press!

Temporal Specificity of Reward Prediction Errors Signaled by Putative Dopamine Neurons in Rat VTA Depends on Ventral Striatum

Neuron Volume 91, Issue 1, p182–193, 6 July 2016

Yuji K. Takahashi, Angela J. Langdon,Yael Niv, and Geoffrey Schoenbaum

Dopamine neurons signal reward prediction errors. This requires accurate reward predictions. It has been suggested that the ventral striatum provides these predictions. Here we tested this hypothesis by recording from putative dopamine neurons in the VTA of rats performing a task in which prediction errors were induced by shifting reward timing or number. In controls, the neurons exhibited error signals in response to both manipulations....

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A figure from this month's paper.
A figure from this month's paper.
Featured paper of the Month!

AUGUST: Role of Ventral Subiculum in Context-Induced Relapse to Alcohol Seeking after Punishment-Imposed Abstinence

J Neurosci. 6 March 2016, 36(11): 3281-3294

Nathan J. Marchant, Erin J. Campbell, Leslie R. Whitaker, Brandon K. Harvey, Konstantin Kaganovsky, Sweta Adhikary, Bruce T. Hope, Robert C. Heins, Thomas E. Prisinzano, Eyal Vardy, Antonello Bonci, Jennifer M. Bossert, andYavin Shaham

In many human alcoholics, abstinence is self-imposed because of the negative consequences of excessive alcohol use, and relapse is often triggered by exposure to environmental contexts associated with prior alcohol drinking. We recently developed a rat model of this human condition in which we train alcohol-preferring P rats to self-administer alcohol in one context (A), punish the alcohol-reinforced responding in a different context (B), and then test for relapse to alcohol seeking in Contexts A and B without alcohol or shock....

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Reviews to Read

The Brain on Drugs: From Reward to Addiction

Nora D. Volkow and Marisela Morales

Advances in neuroscience identified addiction as a chronic brain disease with strong genetic, neurodevelopmental, and sociocultural components. We here discuss the circuit- and cell-level mechanisms of this condition and its co-option of pathways regulating reward, self-control, and affect. Drugs of abuse exert their initial reinforcing effects by triggering supraphysiologic surges of dopamine in the nucleus accumbens that activate the direct striatal pathway via D1 receptors and inhibit the indirect striato-cortical pathway via D2 receptors....

Read the full review at Cell.

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Reviews to Read

Multiplexed neurochemical signaling by neurons of the ventral tegmental area

David J. Barker, David H. Root, Shiliang Zhang, and Marisela Morales

The ventral tegmental area (VTA) is an evolutionarily conserved structure that has roles in reward-seeking, safety-seeking, learning, motivation, and neuropsychiatric disorders such as addiction and depression. The involvement of the VTA in these various behaviors and disorders is paralleled by its diverse signaling mechanisms. Here we review recent advances in our understanding of neuronal diversity in the VTA with a focus on cell phenotypes that participate in 'multiplexed' neurotransmission involving distinct signaling mechanisms....

Read the full review at PubMed.

A figure from this month's paper.
A figure from this month's paper.
Featured paper of the Month!

JULY: Hyperactive somatostatin interneurons contribute to excitotoxicity in neurodegenerative disorders

Nat Neurosci. 2016 Apr;19(4):557-9. Epub 2016 Feb 22.

Wen Zhang, Lifeng Zhang, Bo Liang, David Schroeder, Zhong-wei Zhang, Gregory A Cox, Yun Li, & Da-Ting Lin

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping neurodegenerative disorders whose pathogenesis remains largely unknown. Using TDP-43(A315T) mice, an ALS and FTD model with marked cortical pathology, we found that hyperactive somatostatin interneurons disinhibited layer 5 pyramidal neurons (L5-PNs) and contributed to their excitotoxicity. Focal ablation of somatostatin interneurons efficiently restored normal excitability of L5-PNs and alleviated neurodegeneration, suggesting a new therapeutic target for ALS and FTD....

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The National Institute on Drug Abuse (NIDA), is part of the National Institutes of Health (NIH), the principal biomedical and behavioral research agency of the United States Government. NIH is a component of the U.S. Department of Health and Human Services.

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