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Featured Research Papers

A figure from this study

A figure from this study

Hot off the Press paper!

Chemogenetics revealed: DREADD occupancy and activation via converted clozapine

 

Science. 2017 Aug 4;357(6350):503-507. doi: 10.1126/science.aan2475.

Gomez JL, Bonaventura J, Lesniak W, Mathews WB, Sysa-Shah P, Rodriguez LA, Ellis RJ, Richie CT, Harvey BK, Dannals RF, Pomper MG, Bonci A, Michaelides M.

Designer receptors exclusively activated by designer drugs (DREADDs) constitute a powerful chemogenetic strategy that can modulate nerve cell activity in freely moving animal preparations. NIDA scientists used radioligand receptor occupancy measurements and in vivo positron emission tomography to show that DREADDs expressed in the brain are not activated by the designer compound CNO. Instead, they are activated by the CNO metabolite clozapine, a drug with multiple endogenous targets. This may have important implications for the interpretation of results obtained with this popular technology.

Read more about this paper on PubMed.

Hot off the Press Archives

Photo of Elise Lesage.

Elise Lesage

Hot off the Press paper!

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, which are associated with severity of nicotine dependence but not with the acute effects of nicotine or varenicline tartrate (the drug Chantix), and behavioral and neural signatures of cognitive flexibility, which were impaired in the abstinent state but restored with stimulation of the nicotinic acetylcholine receptors. This means that currently available drug therapies appear to alleviate abstinent smokers’ impaired cognitive flexibility but not reward sensitivity.

Read more about this paper on PubMed.

Hot off the Press Archives

Study authors Haiying Zhang, Zheng-Xiong Xi, and Guohua Bi.

Study authors Haiying Zhang, Zheng-Xiong Xi, and Guohua Bi.

Featured paper of the Month!

August - 2017 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. These findings suggest that JJC8-016 is a unique DAT inhibitor that has no cocaine-like abuse potential by itself. Moreover, pretreatment with JJC8-016 significantly inhibits cocaine-taking and cocaine-seeking behavior likely by interfering with cocaine binding to DAT.

You can read more about this paper on PubMed.

Featured Paper Archives

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A figure from this study.

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. Both dopamine-releasing and non-dopamine-releasing VTA neurons integrate afferent signals with local inhibitory or excitatory inputs to generate particular output firing patterns. Various individual inputs, outputs and local connections have been shown to be sufficient to generate reward- or aversion-related behaviour, indicative of the impressive contribution of this small population of neurons to behaviour.

You can read more about this paper on PubMed.

Reviews to Read Archives

Study authors Agustin Zapata and Eun-Kyung Hwang

Study authors 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 excited a majority of LHb neurons in in vitro electrophysiology experiments. These results indicate that the LHb participates in the suppression of impulsive responding for cocaine through the activation of a cholinergic circuit, and they suggest that LHb dysfunction may contribute to impaired impulse control associated with drug addiction.

You can read more about this paper on PubMed.

Featured Paper Archives

NIDA IRP News

Barry Hoffer
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 Hoffer
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.

Full Story Here.

Women Scientist Advisors Committee Logo

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.

Learn more about the Women Scientist Advisors Committee here.

Tsung-Ping Su

2016 Award for Sustainable Acquisitions - Individual
Dr. Da-Ting Lin has prioritized energy conservation, financial savings, and protecting both human and environmental health through his work.

Full Story Here.

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