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

Critical Role of Peripheral Vasoconstriction in Fatal Brain Hyperthermia Induced by MDMA (Ecstasy) under Conditions That Mimic Human Drug Use

J. Neurosci June 4, 2014 - 34(23):7754–7762

Eugene A. Kiyatkin, Albert H. Kim, Ken T. Wakabayashi, Michael H. Baumann, and Yavin Shaham

MDMA(Ecstasy) is an illicit drug used by young adults at hot, crowed “rave” parties, yet the data on potential health hazards of its abuse remain controversial. Here, we examined the effect of MDMA on temperature homeostasis in male rats under standard laboratory conditions and under conditions that simulate drug use in humans.Wechronically implanted thermocouple microsensors in the nucleus accumbens (a brain reward area), temporal muscle, and facial skin to measure temperature continuously from freely moving rats.

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Two authors from this month's paper, Anton Ilango, and Andrew J. Kesner.
Two authors from this month's paper, Anton Ilango, and Andrew J. Kesner.
Featured paper of the Month!

JUNE: Similar roles of substantia nigra and ventral tegmental dopamine neurons in reward and aversion.

J Neurosci. 2014 Jan 15;34(3):817-22. doi: 10.1523/JNEUROSCI.1703-13.2014

Anton Ilango, Andrew J. Kesner, Kristine L. Keller, Garret D. Stuber, Antonello Bonci, Satoshi Ikemoto.

Dopamine neurons in the ventral tegmental area (VTA) are implicated in affective functions. However, it is unclear to what extent dopamine neurons in substantia nigra pars compacta (SNc) play such roles. TH-Cre transgenic mice received adeno-associated viral vectors encoding channelrhodopsin2 (ChR2), halorhodopsin (NpHR), or control vector into the VTA or SNc, resulting in selective expression of these opsins in dopamine neurons....

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Dr. Elliot Stein. Dr. Elliot Stein.
Reviews to Read

MAY: Dorsal medial prefrontal cortex (MPFC) circuitry in rodent models of cocaine use: implications for drug addiction therapies

Agnes J. Jasinska, Billy T. Chen, Antonello Bonci, & Elliot A. Stein

Although the importance of the medial prefrontal cortex (MPFC) in cocaine addiction is well established, its precise contribution to cocaine seeking, taking and relapse remains incompletely understood. In particular, across two different models of cocaine self-administration, pharmacological or optogenetic activation of the dorsal MPFC has been reported to sometimes promote and sometimes inhibit cocaine seeking. We highlight important methodological differences between the two experimental paradigms and propose a framework to potentially reconcile the apparent discrepancy....

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!

MAY: Real-time tracking of neighborhood surroundings and mood in urban drug misusers: Application of a new method to study behavior in its geographical context

Drug and Alcohol Dependence 134 (2014) 22– 29

David H. Epstein, Matthew Tyburski, Ian M. Craig, Karran A. Phillips, Michelle L. Jobes, Massoud Vahabzadeh, Mustapha Mezghanni, Jia-Ling Lin, C. Debra M. Furr-Holden, Kenzie L. Preston

Background: Maladaptive behaviors may be more fully understood and efficiently prevented by ambula-tory tools that assess people’s ongoing experience in the context of their environment.

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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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