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

AUGUST: Norepinephrine activates dopamine D4 receptors in the rat lateral habenula.

J Neurosci. 2015 Feb 25;35(8):3460-9.

David H. Root, Alexander F. Hoffman, Cameron H. Good, Shiliang Zhang, Eduardo Gigante, Carl R. Lupica, and Marisela Morales

The lateral habenula (LHb) is involved in reward and aversion and is reciprocally connected with dopamine (DA)-containing brain regions, including the ventral tegmental area (VTA). We used a multidisciplinary approach to examine the properties of DA afferents to the LHb in the rat. We find that 90% of VTA tyrosine hydroxylase (TH) neurons projecting to the LHb lack vesicular monoamine transporter 2(VMAT2)mRNA,and there is little coexpression ofTHandVMAT2protein in this mesohabenular pathway.

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Reviews to Read

Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter

Maarten E.A. Reith, Bruce E. Blough, Weimin C. Hong, Kymry T. Jones, Kyle C. Schmitt, Michael H. Baumann, John S. Partilla, Richard B. Rothman, Jonathan L. Katz

Background: Treatment of stimulant-use disorders remains a formidable challenge, and the dopamine transporter (DAT) remains a potential target for antagonist or agonist-like substitution therapies.

Methods: This review focuses on DAT ligands, such as benztropine, GBR 12909, modafinil, and DAT substrates derived from phenethylamine or cathinone that have atypical DAT-inhibitor effects, eitherin vitro or in vivo. The compounds are described from a molecular mechanistic, behavioral, and medicinal–chemical perspective....

Read the full review at PubMed.

A figure from this paper. A figure from this paper.
Reviews to Read

Baths Salts, Spice, and Related Designer Drugs: The Science Behind the Headlines

Michael H. Baumann, Ernesto Solis, Jr., XLucas R. Watterson, Julie A. Marusich, William E. Fantegrossi, and Jenny L. Wiley

The abuse of synthetic psychoactive substances known as “designer drugs,” or “new psychoactive substances” (NPS), is increasing at an alarming rate. NPS are purchased as alternatives to traditional illicit drugs of abuse and are manufactured to circumvent laws regulating the sale and use of controlled substances. Synthetic cathinones (i.e., “bath salts”) and synthetic cannabinoids (i.e., “spice”) are two types of NPS that have received substantial media attention....

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: Basal Hippocampal Activity and Its Functional Connectivity Predicts Cocaine Relapse

Biol Psychiatry. 2015 Jan 30. pii: S0006-3223(15)00045-1

Bryon Adinoff, Hong Gu, Carmen Merrick, Meredith McHugh, Haekyung Jeon-Slaughter, Hanzhang Lu, Yihong Yang, and Elliot A. Stein

BACKGROUND: Cocaine-induced neuroplastic changes may result in a heightened propensity for relapse. Using regional cerebral blood flow (rCBF) as a marker of basal neuronal activity, this study assessed alterations in rCBF and related resting state functional connectivity (rsFC) to prospectively predict relapse in patients following treatment for cocaine use disorder (CUD)....

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Jordi Bonaventura.
Jordi Bonaventura.
Hot off the Press!

Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer

PNAS June 22, 2015, doi: 10.1073/pnas.1507704112

Jordi Bonaventura, Gemma Navarro, Verònica Casadó-Anguera, Karima Azdad, William Rea, Estefanía Moreno, Marc Brugarolas, Josefa Mallol, Enric I. Canela, Carme Lluís, Antoni Cortés, Nora D. Volkow, Serge N. Schiffmann, Sergi Ferré, and Vicent Casadó

Adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromers are key modulators of striatal neuronal function. It has been suggested that the psychostimulant effects of caffeine depend on its ability to block an allosteric modulation within the A2AR-D2R heteromer, by which adenosine decreases the affinity and intrinsic efficacy of dopamine at the D2R....

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Reviews to Read

Role of corticostriatal circuits in context-induced reinstatement of drug seeking

Nathan J.Marchant, Konstantin Kaganovsky, Yavin Shaham, Jennifer M. Bossert

Drug addiction is characterized by persistent relapse vulnerability during abstinence. In abstinent drug users, relapse is often precipitated by re-exposure to environmental contexts that were previously associated with drug use. This clinical scenario is modeled in preclinical studies using the context-induced reinstatement procedure, which is based on the ABA renewal procedure. In these studies, context-induced reinstatement of drug seeking is reliably observed in laboratory animals that were trained to self-administer drugs abused by humans....

Read the full review at PubMed.


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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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