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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Doctor Zuzana Justinova.
Doctor Zuzana Justinova.
Featured paper of the Month!

SEPTEMBER: Differential Effects of Presynaptic versus Postsynaptic Adenosine A2A Receptor Blockade onΔ9-Tetrahydrocannabinol (THC) Self-Administration in Squirrel Monkeys

J Neurosci. 2014 May 7;34(19):6480-4.

Zuzana Justinova, Godfrey H. Redhi, Steven R. Goldberg, and Sergi Ferre

Different doses of an adenosine A2A receptor antagonist MSX-3 [3,7-dihydro-8-[(1E)-2-(3-ethoxyphenyl)ethenyl]-7 methyl-3-[3-(phosphooxy)propyl-1-(2 propynil)-1H-purine-2,6-dione] were found previously to either decrease or increase self-administration of cannabinoids delta-9-tetrahydrocannabinol (THC) or anandamide in squirrel monkeys. It was hypothesized that the decrease observed with a relatively low dose of MSX-3 was related to blockade of striatal presynaptic A2A receptors that modulate glutamatergic neurotransmission....

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

AUGUST: Gangliosides and Ceramides Change in a Mouse Model of Blast Induced Traumatic Brain Injury

ACS Chem. Neurosci., 2013, 4 (4), pp 594–600

Amina S. Woods, Benoit Colsch, Shelley N. Jackson, Jeremy Post, Kathrine Baldwin, Aurelie Roux, Barry Hoffer, Brian M. Cox, Michael Hoffer, Vardit Rubovitch, Chaim G. Pick, J. Albert Schultz, and Carey Balaban.

Explosive detonations generate atmospheric pressure changes that produce nonpenetrating blast induced “mild” traumatic brain injury (bTBI). The structural basis for mild bTBI has been extremely controversial. The present study applies matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging to track the distribution of gangliosides in mouse brain tissue that were exposed to very low level of explosive detonations (2.5−5.5 psi peak overpressure)....

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Dr. Federica Lucantonio. Dr. Federica Lucantonio.
Hot off the Press!

Orbitofrontal activation restores insight lost after cocaine use

Nature Neuroscience (2014) doi:10.1038/nn.3763

Federica Lucantonio, Yuji K Takahashi, Alexander F Hoffman, Chun Chang, Sheena Bali-Chaudhary, Yavin Shaham, Carl R Lupica, & Geoffrey Schoenbaum

Addiction is characterized by a lack of insight into the likely outcomes of one’s behavior. Insight, or the ability to imagine outcomes, is evident when outcomes have not been directly experienced. Using this concept, work in both rats and humans has recently identified neural correlates of insight in the medial and orbital prefrontal cortices. We found that these correlates were selectively abolished in rats by cocaine self-administration....

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

JULY: Personality traits and vulnerability or resilience to substance use disorders.

Annabelle M. Belcher, Nora D. Volkow, F. Gerard Moeller, and Sergi Ferre

Clear evidence supports a genetic basis for substance use disorders (SUD). Yet, the search to identify individual gene contributions to SUD has been unsuccessful. Here, we argue for the study of endophenotypes within the frame of individual differences, and identify three highorder personality traits that are tied to specific brain systems and genes, and that offer a tractable approach to studying SUD. These personality traits, and the genes that moderate them, interact dynamically with the environment and with the drugs themselves to determine ultimately an individual’s vulnerability or resilience to developing SUD....

Read the full review at PubMed.

Two authors from this month's paper, Oluyomi M. Okunola-Bakare, and Jianjing Cao
Two authors from this month's paper, Oluyomi M. Okunola-Bakare, and Jianjing Cao
Featured paper of the Month!

JULY: Elucidation of Structural Elements for Selectivity across Monoamine Transporters: Novel 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues

J Med Chem 2014, 57, 1000-1013

Oluyomi M. Okunola-Bakare, Jianjing Cao, Theresa Kopajtic, Jonathan L. Katz, Claus J. Loland, Lei Shi, and Amy Hauck Newman.

2-[(Diphenylmethyl)sulfinyl]acetamide (modafinil, (±)-1) is a unique dopamine uptake inhibitor that binds the dopamine transporter (DAT) differently than cocaine and may have potential for the treatment of psychostimulant abuse. To further investigate structural requirements for this divergent binding mode, novel thio- and sulfinylacetamide and ethanamine analogues of (±)-1 were synthesized wherein (1) the diphenyl rings were substituted with methyl, trifluoromethyl, and halogen substituents and (2) substituents were added to the terminal amide/amine nitrogen....

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An author from this month's paper. An author from this month's paper.
Hot off the Press!

Orbitofrontal neurons infer the value and identity of predicted outcomes

Nature Communications 5:3926 | DOI: 10.1038/ncomms4926

Thomas A. Stalnaker, Nisha K. Cooch2, Michael A. McDannald, Tzu-Lan Liu, Heather Wied & Geoffrey Schoenbaum

The best way to respond flexibly to changes in the environment is to anticipate them. Such anticipation often benefits us if we can infer that a change has occurred, before we have actually experienced the effects of that change. Here we test for neural correlates of this process by recording single-unit activity in the orbitofrontal cortex in rats performing a choice task in which the available rewards changed across blocks of trials. Consistent with the proposal that orbitofrontal cortex signals inferred information, firing changes at the start of each new block as if predicting the not-yet-experienced reward....

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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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