Featured Research Papers - The Intramural Research Program of the National Institute on Drug Abuse

Skip Navigation

Featured Research Papers

A figure from this month's paper.
A figure from this month's paper.

Featured Paper Archives
Featured paper of the Month!

November's Featured Paper!

Impaired functional connectivity within and between frontostriatal circuits and its association with compulsive drug use and trait impulsivity in cocaine addiction.

JAMA Psychiatry 2015 Jun;72(6):584-92

Hu Y, Salmeron BJ, Gu H, Stein EA, Yang Y.

IMPORTANCE: Converging evidence has long identified both impulsivity and compulsivity as key psychological constructs in drug addiction. Although dysregulated striatal-cortical network interactions have been identified in cocaine addiction, the association between these brain networks and addiction is poorly understood.

OBJECTIVES: To test the hypothesis that cocaine addiction is associated with disturbances in striatal-cortical communication as captured by resting-state functional connectivity (rsFC), measured from coherent spontaneous fluctuations in the blood oxygenation level-dependent functional magnetic resonance imaging signal, and to explore the relationships between striatal rsFC, trait impulsivity, and uncontrolled drug use in cocaine addiction.

A case-control, cross-sectional study was conducted at the National Institute on Drug Abuse Intramural Research Program outpatient magnetic resonance imaging facility. Data used in the present study were collected between December 8, 2005, and September 30, 2011. Participants included 56 non-treatment-seeking cocaine users (CUs) (52 with cocaine dependence and 3 with cocaine abuse) and 56 healthy individuals serving as controls (HCs) matched on age, sex, years of education, race, estimated intelligence, and smoking status.

MAIN OUTCOMES AND MEASURES: Voxelwise statistical parametric analysis testing the rsFC strength differences between CUs and HCs in brain regions functionally connected to 6 striatal subregions defined a priori.

RESULTS: Increased rsFC strength was observed predominantly in striatal-frontal circuits; decreased rsFC was found between the striatum and cingulate, striatal, temporal, hippocampal/amygdalar, and insular regions in the CU group compared with the HCs. Increased striatal-dorsal lateral prefrontal cortex connectivity strength was positively correlated with the amount of recent cocaine use (uncorrected P < .046) and elevated trait impulsivity in the CUs (uncorrected P < .012), and an index reflecting the balance between striatal-dorsal anterior cingulate cortex and striatal-anterior prefrontal/orbitofrontal cortex circuits was significantly associated with loss of control over cocaine use (corrected P < .012).

CONCLUSIONS AND RELEVANCE: Cocaine addiction is associated with disturbed rsFC in several specific striatal-cortical circuits. Specifically, compulsive cocaine use, a defining characteristic of dependence, was associated with a balance of increased striatal-anterior prefrontal/orbitofrontal and decreased striatal-dorsal anterior cingulate connectivity; trait impulsivity, both a risk factor for and a consequence of cocaine use, was associated with increased dorsal striatal-dorsal lateral prefrontal cortex connectivity uniquely in CUs. These findings provide new insights toward the neurobiological mechanisms of addiction and suggest potential novel therapeutic targets for treatment.

You can read more about this paper at the website for PubMed.

October's Featured Paper!

Mechanism of the Association between Na+ Binding and Conformations at the Intracellular Gate in Neurotransmitter: Sodium Symporters

J Biol Chem. VOL. 290, NO. 22, pp. 13992–14003, May 29, 2015

Sebastian Stolzenberg, Matthias Quick, Chunfeng Zhao, Kamil Gotfryd, George Khelashvili, Ulrik Gether, Claus J. Loland, Jonathan A. Javitch, Sergei Noskov, Harel Weinstein, and Lei Shi

You can read more about this paper at the website for PubMed.

September's Featured Paper!

Incubation of methamphetamine craving is associated with selective increases in expression of Bdnf and Trkb, glutamate receptors, and epigenetic enzymes in cue-activated fos-expressing dorsal striatal neurons.

J Neurosci. 2015 May 27;35(21):8232-44.

Xuan Li, F. Javier Rubio, Tamara Zeric, Jennifer M. Bossert, Sarita Kambhampati, Hannah M. Cates, Pamela J. Kennedy, Qing-Rong Liu, Raffaello Cimbro, Bruce T. Hope, Eric J. Nestler, and Yavin Shaham

You can read more about this paper at the website for PubMed.

Related Information...

IRP Training Opportunities...

2009 Postbacs
Postdoc, Predoc, Postbac and Summer Student training opportunities available!

2009 Summer Students
Research & Training Program for Under-represented Populations

A figure from this paper.
A figure from this paper.

Hot off the Press Archives
Featured paper of the Month!

Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatinremodeling factors at the nuclear envelope

Proc Natl Acad Sci USA. 2015 Nov 9. pii: 201518894. [Epub ahead of print]

Shang-Yi A. Tsai, Jian-Ying Chuang, Meng-Shan Tsia, Xiao-fei Wang, Zheng-Xiong Xi, Jan-Jong Hung, Wen-Chang Chang, Antonello Bonci, and Tsung-Ping Su

The sigma-1 receptor (Sig-1R) chaperone at the endoplasmic reticulum (ER) plays important roles in cellular regulation. Here we found a new function of Sig-1R, in that it translocates from the ER to the nuclear envelope (NE) to recruit chromatin-remodeling molecules and regulate the gene transcription thereof. Sig-1Rs mainly reside at the ER–mitochondrion interface. However, on stimulation by agonists such as cocaine, Sig-1Rs translocate from ER to the NE, where Sig-1Rs bind NE protein emerin and recruit chromatin-remodeling molecules, including lamin A/C, barrier-to-autointegration factor (BAF), and histone deacetylase (HDAC), to form a complex with the gene repressor specific protein 3 (Sp3). Knockdown of Sig-1Rs attenuates the complex formation. Cocaine was found to suppress the gene expression of monoamine oxidase B (MAOB) in the brain of wild-type but not Sig-1R knockout mouse. A single dose of cocaine (20 mg/kg) in rats suppresses the level of MAOB at nuclear accumbens without affecting the level of dopamine transporter. Daily injections of cocaine in rats caused behavioral sensitization. Withdrawal from cocaine in cocaine-sensitized rats induced an apparent time-dependent rebound of theMAOB protein level to about 200% over control on day 14 after withdrawal. Treatment of cocaine-withdrawn rats with the MAOB inhibitor deprenyl completely alleviated the behavioral sensitization to cocaine. Our results demonstrate a role of Sig-1R in transcriptional regulation and suggest cocaine may work through this newly discovered genomic action to achieve its addictive action. Results also suggest theMAOB inhibitor deprenyl as a therapeutic agent to block certain actions of cocaine during withdrawal.

More about this paper

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

More about this paper

Sigma-1 receptor regulates Tau phosphorylation and axon extension by shaping p35 turnover via myristic acid

PNAS May 11, 2015, doi: 10.1073/pnas.1422001112

Shang-Yi A. Tsai, Michael J. Pokrass, Neal R. Klauer, Hiroshi Nohara, and Tsung-Ping Su

More about this paper

Health and Human Services Logo National Institute on Drug Abuse Logo

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.

PDF documents require the free Adobe Reader. Microsoft Word documents require the free Microsoft Word viewer. Microsoft PowerPoint documents require the free Microsoft PowerPoint viewer. Flash content requires the free Adobe Flash Player.