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Elise Lesage
Elise Lesage

hot off the press!

Neural Signatures of Cognitive Flexibility and Reward Sensitivity Following Nicotinic Receptor Stimulation in Dependent Smokers: A Randomized Trial.

JAMA Psychiatry. 2017 Jun 1;74(6):632-640. doi: 10.1001/jamapsychiatry.2017.0400.

Lesage E, Aronson SE, Sutherland MT, Ross TJ, Salmeron BJ, Stein EA.

In this paper, NIDA scientists wanted to answer the question : ”How are reward sensitivity, in brain regions thought to be involved in drug abuse, and cognitive flexibility affected by acute abstinence and stimulation of the nicotinic acetylcholine receptors in dependent smokers?” In this placebo-controlled crossover study they found a “double dissociation” between decreased neural signatures of reward sensitivity...

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Study authors Study authors Haiying Zhang, Zheng-Xiong Xi, and Guohua Bi.
Haiying Zhang, Zheng-Xiong Xi, Guohua Bi.
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The Novel Modafinil Analog, JJC8-016, as a Potential Cocaine Abuse Pharmacotherapeutic

Neuropsychopharmacology. 2017 Aug;42(9):1871-1883. doi: 10.1038/npp.2017.41. Epub 2017 Mar 7.

Zhang HY, Bi GH, Yang HJ, He Y, Xue G, Cao J, Tanda G, Gardner EL, Newman AH, Xi ZX.

JJC8-016, a recently discovered (±) modafinil analogue and atypical dopamine transporter (DAT) inhibitor, was compared to R-modafinil for its effects in several rodent models of psychostimulant abuse. Strikingly, pretreatment with JJC8-016 dose-dependently inhibited cocaine-enhanced locomotion, cocaine self-administration, and cocaine-induced reinstatement of drug-seeking behavior, while R-MOD inhibited cocaine-induced reinstatement only at the high dose of 100 mg/kg. Notably, JJC8-016 alone neither altered extracellular dopamine in the nucleus accumbens nor maintained self-administration. It also failed to induce reinstatement of drug-seeking behavior ...

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Study authors Vikek Kumar and Amy Moritz.
Vikek Kumar and Amy Moritz.
Featured paper of the Month!

July 2017 - Synthesis and Pharmacological Characterization of Novel trans-Cyclopropylmethyl-Linked Bivalent Ligands That Exhibit Selectivity and Allosteric Pharmacology at the Dopamine D3 Receptor (D3R).

J Med Chem. 2017 Feb 23;60(4):1478-1494. doi: 10.1021/acs.jmedchem.6b01688. Epub 2017 Feb 10.

Kumar V, Moritz AE, Keck TM, Bonifazi A, Ellenberger MP, Sibley CD, Free RB, Shi L, Lane JR, Sibley DR, Newman AH.

The development of bitopic ligands directed toward D2-like receptors has proven to be of particular interest to improve the selectivity and/or affinity of these ligands and as an approach to modulate and bias their efficacies. The structural similarities between dopamine D3 receptor (D3R)-selective molecules that display bitopic or allosteric pharmacology and those that are simply competitive antagonists are subtle and intriguing...

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Reviews to Read

June 2017 - Ventral tegmental area: cellular heterogeneity, connectivity and behaviour

Nat Rev Neurosci. 2017 Feb;18(2):73-85. doi: 10.1038/nrn.2016.165. Epub 2017 Jan 5. Review.

Morales M, Margolis EB.

Dopamine-releasing neurons of the ventral tegmental area (VTA) have central roles in reward-related and goal-directed behaviours. VTA dopamine-releasing neurons are heterogeneous in their afferent and efferent connectivity and, in some cases, release GABA or glutamate in addition to dopamine. Recent findings show that motivational signals arising from the VTA can also be carried by non-dopamine-releasing projection neurons, which have their own specific connectivity...

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Photo of 2017 Mentoring Award winners (left to right): Geoffrey Schoenbaum, MD, PhD (Investigator Award); Lindsay De Biase, PhD (Postdoctoral Fellow Award); and Karran Phillips, MD (Staff Clinician Award).
2017 Mentoring Awardees

NIDA IRP NEWS!

Congratulations to the 2017 NIDA IRP Mentoring Award winners.

Award recipients are (left to right): Geoffrey Schoenbaum, MD, PhD (Investigator Award); Lindsay De Biase, PhD (Postdoctoral Fellow Award); and Karran Phillips, MD (Staff Clinician Award). They were presented with plaques at the 6th annual NIDA Poster Day and Mentoring Awards Ceremony on May 17, 2017.

The Mentoring Awards recognize individuals who have served as exceptional mentors to trainees in the institute, and are given annually in the spring.

More about our Research Training program here

Barry J. Hoffer Receiving the Award
Barry J. Hoffer Receiving the Award

NIDA IRP NEWS!

Barry J. Hoffer awarded Honorary Doctors of the Faculty of Philosophy at the University of Helsinki

Dr. Barry J. Hoffer, the former Scientific Director of the NIDA IRP, has been awarded an Honorary Doctors of the Faculty of Philosophy from the University of Helsinki for his lifelong work in neuropharmacology. The Faculty of Philosophy of the University of Helsinki confers distinguished persons from the fields of science, culture and society as honorary doctors each year May. Angela Merkel was also among this year's award recipients.

More information here

Agustin Zapata and Eun-Kyung Hwang

Agustin Zapata and Eun-Kyung Hwang
Featured paper of the Month!

June 2017 - Lateral Habenula Involvement in Impulsive Cocaine Seeking

Neuropsychopharmacology. 2017 Apr;42(5):1103-1112. doi: 10.1038/npp.2016.286. Epub 2016 Dec 27.

Zapata A, Hwang EK, Lupica CR.

The lateral habenula (LHb) is a brain structure involved in sleep control, reward-based decision making, avoidance of punishment, and responses to stress. Additional work has established that the LHb mediates negative feedback in response to aversive events. As a hallmark of drug addiction is the inability to limit drug use despite negative consequences, we hypothesize that LHb dysfunction may have a role in lack of control over drug seeking. We find that inhibition of the LHb did not alter suppression of cocaine self-administration in response to punishment nor cocaine’s reinforcing efficacy. However, LHb inhibition increased cocaine seeking when the drug was not available in rats trained to discriminate its presence using an environmental cue. This effect was mimicked by intra-LHb muscarinic cholinergic (mAch) antagonist injection, and activation of mACh receptors ...

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Reviews to Read

Computational approaches to detect allosteric pathways in transmembrane molecular machines

Biochim Biophys Acta. 2016 Jul;1858(7 Pt B):1652-62. doi: 10.1016/j.bbamem.2016.01.010. Epub 2016 Jan 22.

Stolzenberg S, Michino M, LeVine MV, Weinstein H, Shi L.

Many of the functions of transmembrane proteins involved in signal processing and transduction across the cell membrane are determined by allosteric couplings that propagate the functional effects well beyond the original site of activation. Data gathered from breakthroughs in biochemistry, crystallography, and single molecule fluorescence have established a rich basis of information for the study of molecular mechanisms in the allosteric couplings of such transmembrane proteins. The mechanistic details of these couplings...

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2017 WSA Award Winners.

NIDA IRP NEWS!

Congratulations to the 2017 Women Scientist Advisors Committee award winners at the NIDA IRP!

This year's winners at the NIDA IRP are Lindsay De Biase (Postdoctoral Fellow), Jayanthi Sankar (Staff Scientist) and Marisela Morales (Investigator). The winners were presented with trophies at the Biomedical Research Center this month.

The WSA awards recognize women scientists at NIDA for their scientific accomplishments.

Learn more about the Women Scientist Advisors Committee here.

Study authors William Rea, Ning Sheng Cai and Cesar Quiroz-Molina
William Rea, Ning Sheng Cai and
Cesar Quiroz-Molina
Featured paper of the Month!

May: Functional μ-Opioid-Galanin Receptor Heteromers in the Ventral Tegmental Area

J Neurosci. 2017 Feb 1;37(5):1176-1186. doi: 10.1523/JNEUROSCI.2442-16.2016. Epub 2016 Dec 22.

Moreno E, Quiroz C, Rea W, Cai NS, Mallol J, Cortés A, Lluís C, Canela EI, Casadó V, Ferré S.

The ventral tegmental area (VTA) receives phenotypically distinct innervations from the pedunculopontine tegmental nucleus (PPTg). While PPTg-to-VTA inputs are thought to play a critical role in stimulus-reward learning, direct evidence linking PPTg-to-VTA phenotypically distinct inputs in the learning process remains lacking. Here, we used optogenetic approaches to investigate the functional contribution of PPTg excitatory and inhibitory inputs to the VTA in appetitive Pavlovian conditioning....

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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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