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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  • Our Research

    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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A figure from this month's review. A figure from this month's review.
Reviews to Read

MARCH: G Protein–Coupled Receptor Oligomerization Revisited: Functional and Pharmacological Perspectives

Sergi Ferré, Vicent Casadó, Lakshmi A. Devi, Marta Filizola, Ralf Jockers, Martin J. Lohse, Graeme Milligan, Jean-Philippe Pin, and Xavier Guitart

Most evidence indicates that, as for family C G protein–coupled receptors (GPCRs), family A GPCRs form homo- and heteromers. Homodimers seem to be a predominant species, with potential dynamic formation of higher-order oligomers, particularly tetramers. Although monomeric GPCRs can activate G proteins, the pentameric structure constituted by one GPCR homodimer and one heterotrimeric G protein may provide a main functional unit, and oligomeric entities can be viewed as multiples of dimers.....

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!

MARCH: Large-Scale Brain Networks in the Awake, Truly Resting Marmoset Monkey

The Journal of Neuroscience, 16 October 2013, 33(42): 16796-16804

Annabelle M. Belcher, Cecil C. Yen, Haley Stepp, Hong Gu, Hanbing Lu, Yihong Yang, Afonso C. Silva, and Elliot A. Stein

Resting-state functional MRI is a powerful tool that is increasingly used as a noninvasive method for investigating whole-brain circuitry and holds great potential as a possible diagnostic for disease. Despite this potential, few resting-state studies have used animal models (of which nonhuman primates represent our best opportunity of understanding complex human neuropsychiatric disease), and no work has characterized networks in awake, truly resting animals....

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A figure from this month's review. A figure from this month's review.
Reviews to Read

FEBRUARY: Neuropathology of substance use disorders

Jean Lud Cadet, Veronica Bisagno, Christopher Mark Milroy

Addictions to licit and illicit drugs are chronic relapsing brain disorders that affect circuits that regulate reward, motivation, memory, and decision-making. Drug-induced pathological changes in these brain regions are associated with characteristic enduring behaviors that continue despite adverse biopsychosocial consequences. Repeated exposure to these substances leads to egocentric behaviors that focus on obtaining the drug by any means and on taking the drug under adverse psychosocial and medical conditions....

Read the full review at PubMed.

A figure from this month's paper. A figure from this month's paper.
Hot off the Press!

Presynaptic glycine receptors as a potential therapeutic target for hyperekplexia disease

Nature Neuroscience 17, 232–239 (2014)

Wei Xiong, Shao-Rui Chen, Liming He, Kejun Cheng, Yi-Lin Zhao, Hong Chen, De-Pei Li, Gregg E Homanics, John Peever, Kenner C Rice, Ling-gang Wu, Hui-Lin Pan & Li Zhang

Although postsynaptic glycine receptors (GlyRs) as αβ heteromers attract considerable research attention, little is known about the role of presynaptic GlyRs, likely α homomers, in diseases. Here, we demonstrate that dehydroxylcannabidiol (DH-CBD), a nonpsychoactive cannabinoid, can rescue GlyR functional deficiency and exaggerated acoustic and tactile startle responses in mice bearing point mutations in α1 GlyRs that are responsible for a hereditary startle-hyperekplexia disease....

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

FEBRUARY: Dopamine D4 Receptor Excitation of Lateral Habenula Neurons via Multiple Cellular Mechanisms

The Journal of Neuroscience, October 23, 2013 • 33(43):16853–16864 • 16853

Cameron H. Good, Huikun Wang, Yuan-Hao Chen, Carlos A. Mejias-Aponte, Alexander F. Hoffman, and Carl R. Lupica

Glutamatergic lateral habenula (LHb) output communicates negative motivational valence to ventral tegmental area (VTA) dopamine (DA) neurons via activation of the rostromedial tegmental nucleus (RMTg). However, the LHb also receives a poorly understood DA input from the VTA, which we hypothesized constitutes an important feedback loop regulating DA responses to stimuli. Using whole-cell electrophysiology in rat brain slices, we find that DA initiates a depolarizing inward current (IDAi) and increases spontaneous firing in 32% of LHb neurons....

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This paper's lead authors.
This paper's lead authors.
Featured paper of the Month!

JANUARY: Resting-State Glutamate and GABA Concentrations Predict Task-Induced Deactivation in the Default Mode Network

J. NEUROSCI 20 November 2013, 33(47): 18566-18573

Yuzheng Hu, Xi Chen, Hong Gu, and Yihong Yang

Deactivation of the human brain’s default mode network (DMN) is regarded as suppression of endogenous activity to support exogenous task-related processes. This phenomenon has important functional relevance and insufficient DMN deactivation has been implicated in several neuropsychiatric disorders. However, the neurochemical mechanism of the DMN's deactivation remains largely unknown. In the present study, we test the hypothesis that the major excitatory and inhibitory neurotransmitters, glutamate and GABA, respectively, are associated with DMN deactivation....

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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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