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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Reviews to Read

APRIL: Using c-fos to study neuronal ensembles in corticostriatal circuitry of addiction

Fabio C. Cruz, F.Javier Rubio, Bruce T. Hope

Learned associations between drugs and environment play an important role in addiction and are thought to be encoded within specific patterns of sparsely distributed neurons called neuronal ensembles. This hypothesis is supported by correlational data from in vivo electrophysiology and cellular imaging studies in relapse models in rodents. In particular, cellular imaging with the immediate early gene c-fos and its protein product Fos has been used to identify sparsely distributed neurons that were strongly activated during conditioned drug behaviors such as drug self-administration and context- and cue-induced reinstatement of drug seeking....

Read the full review at PubMed.

A figure from this paper. A figure from this paper.
Hot off the Press!

Mesopontine median raphe regulates hippocampal ripple oscillation and memory consolidation

Nat Neurosci. 2015 Apr 13. doi: 10.1038/nn.3998. [Epub ahead of print]

Dong V Wang, Hau-Jie Yau, Carl J Broker, Jen-Hui Tsou, Antonello Bonci, and Satoshi Ikemoto

Sharp wave-associated field oscillations (~200 Hz) of the hippocampus, referred to as ripples, are believed to be important for consolidation of explicit memory. Little is known about how ripples are regulated by other brain regions. We found that the median raphe region (MnR) is important for regulating hippocampal ripple activity and memory consolidation. We performed in vivo simultaneous recording in the MnR and hippocampus of mice and found that, when a group of MnR neurons was active, ripples were absent. Consistently, optogenetic stimulation of MnR neurons suppressed ripple activity and inhibition of these neurons increased ripple activity....

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Hot off the Press!

Clonidine Maintenance Prolongs Opioid Abstinence and Decouples Stress From Craving in Daily Life: A Randomized Controlled Trial With Ecological Momentary Assessment

Am J Psychiatry. 2015 Mar 17:appiajp201414081014. [Epub ahead of print]

Kowalczyk WJ, Phillips KA, Jobes ML, Kennedy AP, Ghitza UE, Agage DA, Schmittner JP, Epstein DH, Preston KL.

Objective: Theauthors testedwhetherclonidineblocks stressinduced seeking of heroin and cocaine. The study was also intended to confirm translational findings from a rat model of drug relapse by using ecological momentary assessment of patients’ stress to test hypotheses about clonidine’s behavioral mechanism of action.

Method: The authors conducted a randomized double-blind placebo-controlled clinical trial with 208 opioid-dependent patients at an outpatient buprenorphine clinic....

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The cover from this month's paper.
The cover from this month's paper.
Featured paper of the Month!

APRIL: An in vitro model of human neocortical development using pluripotent stem cells: cocaine-induced cytoarchitectural alterations

DMM 2014 vol. 7 no. 12 1397-1405

Abigail A. Kindberg, Raphael M. Bendriem, Charles E. Spivak, Jia Chen, Annelie Handreck, Carl R. Lupica, Jinny Liu, William J. Freed, and Chun-Ting Lee

Neocortical development involves ordered specification of forebrain cortical progenitors to various neuronal subtypes, ultimately forming the layered cortical structure. Modeling of this process using human pluripotent stem cells (hPSCs) would enable mechanistic studies of human neocortical development, while providing new avenues for exploration of developmental neocortical abnormalities. Here, we show that preserving hPSCs aggregates – allowing embryoid body formation – while adding basic fibroblast growth factor (bFGF) during neuroepithelial development generates neural rosettes showing dorsal forebrain identity....

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Reviews to Read

MARCH: Sigma-1 receptor chaperones in neurodegenerative and psychiatric disorders

Shang-Yi A Tsai, Michael J Pokrass, Neal R Klauer, Nicole E De Credico, and Tsung-Ping Su

Introduction: Sigma-1 receptors (Sig-1Rs) are molecular chaperones that reside mainly in the endoplasmic reticulum (ER) but exist also in the proximity of the plasma membrane. Sig-1Rs are highly expressed in the CNS and are involved in many cellular processes including cell differentiation, neuritogenesis, microglia activation, protein quality control, calcium-mediated ER stress and ion channel modulation. Disturbance in any of the above cellular processes can accelerate the progression of many neurological disorders; therefore, the Sig-1R has been implicated in several neurological diseases....

Read the full review at PubMed.

Dr. Xavier Guitart
Dr. Xavier Guitart
Featured paper of the Month!

MARCH: Functional selectivity of allosteric interactions within G protein-coupled receptor oligomers: the dopamine D1-D3 receptor heterotetramer.

Mol Pharmacol. 2014 Oct;86(4):417-29.

Xavier Guitart, Gemma Navarro, Estefania Moreno, Hideaki Yano, Ning-Sheng Cai, Marta Sánchez-Soto, Sandeep Kumar-Barodia, Yamini T. Naidu, Josefa Mallol, Antoni Cortés, Carme Lluís, Enric I. Canela, Vicent Casadó, Peter J. McCormick, and Sergi Ferré

The dopamine D1 receptor-D3 receptor (D1R-D3R) heteromer is being considered as a potential therapeutic target for neuropsychiatric disorders. Previous studies suggested that this heteromer could be involved in the ability of D3R agonists to potentiate locomotor activation induced by D1R agonists. It has also been postulated that its overexpression plays a role in L-dopa-induced dyskinesia and in drug addiction....

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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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