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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Dr. Stephen Heishman

Associate Director for Education & Training
Postdoc, Predoc, Postbac
and Summer Student training
opportunities available

Image of Dr. Jean Lud Cadet

Dr. Jean Lud Cadet

Associate Director for Diversity and Outreach
Diversity and Outreach Program

Fellowship for Diversity
in Research available!
A figure from this month's Review A figure from this month's Review
Reviews to Read

JANUARY: The sigma-1 receptor: roles in neuronal plasticity and disease

Sigma-1 receptors (Sig-1Rs) have been implicated in many neurological and psychiatric conditions. Sig-1Rs are intracellular chaperones that reside specifically at the endoplasmic reticulum (ER) mitochondrion interface, referred to as the mitochondrion-associated ER membrane (MAM). Here, Sig-1Rs regulate ER mitochondrion Ca2+ signaling. In this review, we discuss the current understanding of Sig-1R functions. Based on this, we suggest that the key cellular mechanisms linking Sig-1Rs to neurological disorders involve the translocation of Sig-1Rs from the MAM to other parts of the cell, whereby Sig-1Rs bind and modulate the activities of various ion channels, receptors, or kinases. Thus, Sig-1Rs and their associated ligands may represent new avenues for treating aspects of neurological and psychiatric diseases....

Read the full review at ScienceDirect.

Figure describing this paper's research. Figure describing this paper's research.
Hot off the Press!

Dynamic Interaction between Sigma-1 Receptor and Kv1.2 Shapes Neuronal and Behavioral Responses to Cocaine

Cell 2013 Jan 17;152(1-2):236-47. doi: 10.1016/j.cell.2012.12.004.

Kourrich S, Hayashi T, Chuang JY, Tsai SY, Su TP, Bonci A.

The sigma-1 receptor (Sig-1R), an endoplasmic reticulum (ER) chaperone protein, is an interorganelle signaling modulator that potentially plays a role in drug-seeking behaviors. However, the brain site of action and underlying cellular mechanisms remain unidentified. We found that cocaine exposure triggers a Sig-1R-dependent upregulation of D-type K+ current in the nucleus accumbens (NAc) that results in neuronal hypoactivity and thereby enhances behavioral cocaine response....

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The bath salt ingredient MDPV is a potent blocker of dopamine uptake in brain tissue.
The bath salt ingredient MDPV is a potent blocker of dopamine uptake
Featured paper of the Month!

JANUARY: Powerful Cocaine-Like Actions of 3,4-Methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive Bath Salts  Products

Neuropsychopharmacology advance online publication, 17 October 2012; doi:10.1038/npp.2012.204

Michael H Baumann, John S Partilla, Kurt R Lehner, Eric B Thorndike Alexander F Hoffman, Marion Holy, Richard B Rothman, Steven R Goldberg, Carl R Lupica, Harald H Sitte, Simon D Brandt, Srihari R Tella, Nicholas V Cozzi, Charles W Schindler

The abuse of psychoactive ‘bath salts’ containing cathinones such as 3,4-methylenedioxypyrovalerone (MDPV) is a growing public health concern, yet little is known about their pharmacology. Here, we evaluated the effects of MDPV and related drugs using molecular, cellular, and whole-animal methods....

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Drs. Bonci and Britt, authors Drs. Bonci and Britt, authors
Hot off the Press!

Synaptic and behavioral profile of multiple glutamatergic inputs to the nucleus accumbens.

Neuron 2012 Nov 21;76(4):790-803. doi: 10.1016/j.neuron.2012.09.040.

Britt JP, Benaliouad F, McDevitt RA, Stuber GD, Wise RA, Bonci A.

Excitatory afferents to the nucleus accumbens (NAc) are thought to facilitate reward seeking by encoding reward-associated cues. Selective activation of different glutamatergic inputs to the NAc can produce divergent physiological and behavioral responses, but mechanistic explanations for these pathway-specific effects are lacking. Here, we compared the innervation patterns and synaptic properties of ventral hippocampus, basolateral amygdala, and prefrontal cortex input to the NAc. Ventral hippocampal input was found to be uniquely localized to the medial NAc shell, where it was predominant and selectively potentiated after cocaine exposure....

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Biological Psychiatry
Biological Psychiatry
Featured paper of the Month!

DECEMBER: R-Modafinil (Armodafinil): A Unique Dopamine Uptake Inhibitor and Potential Medication for Psychostimulant Abuse

Biol. Psych., 2012;72:405 413

Claus J. Loland, Maddalena Mereu, Oluyomi M. Okunola, Jianjing Cao, Thomas E. Prisinzano, Sonia Mazier, Theresa Kopajtic, Lei Shi, Jonathan L. Katz, Gianluigi Tanda, Amy Hauck Newman

Background: (±)-Modafinil has piqued interest as a treatment for attention-deficit/hyperactivity disorder and stimulant dependence. The R-enantiomer of modafinil might have unique pharmacological properties that should be further investigated....

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Dr. Geoffrey Schoenbaum Dr. Geoffrey Schoenbaum, author
Hot off the Press!

Orbitofrontal Cortex Supports Behavior and Learning Using Inferred But Not Cached Values

SCIENCE 16 November 2012: Vol. 338 no. 6109 pp. 953-956

Joshua L. Jones, Guillem R. Esber, Michael A. McDannald, Aaron J. Gruber, Alex Hernandez, Aaron Mirenzi, Geoffrey Schoenbaum

Computational and learning theory models propose that behavioral control reflects value that is both cached (computed and stored during previous experience) and inferred (estimated on the fly on the basis of knowledge of the causal structure of the environment). The latter is thought to depend on the orbitofrontal cortex. Yet some accounts propose that the orbitofrontal cortex contributes to behavior by signaling economic  value, regardless of the associative basis of the information. We found that the orbitofrontal cortex is critical for both value-based behavior and learning when value must be inferred but not when a cached value is sufficient. The orbitofrontal cortex is thus fundamental for accessing model-based representations of the environment to compute value rather than for signaling value per se....

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