Featured Paper of the Month

Featured Paper of the Month – Apil 2020
Published in Elife by Nakamura, Yoki; Dryanovski, Dilyan I; Kimura, Yuriko; Jackson, Shelley N; Woods, Amina S; Yasui, Yuko; Tsai, Shang-Yi; Patel, Sachin; Covey, Daniel P; Su, Tsung-Ping; Lupica, Carl R

By studying brain tissue and neurons in vitro, Nakamura, Dryanovski et al. show that cocaine stimulates the release of endocannabinoids via extracellular vesicles. In essence, cocaine causes neurons to synthesize endocannabinoids that are then enclosed within membrane-bound packages. These packages – or extracellular vesicles – can then fuse with the cell’s membrane. Multiple protein interactions are necessary to permit this extracellular vesicle release, and the authors show that disrupting these control points prevents vesicle release…

Featured Paper of the Month – March 2020
Published in Elife by Stalnaker, Thomas A; Howard, James D; Takahashi, Yuji K; Gershman, Samuel J; Kahnt, Thorsten; Schoenbaum, Geoffrey

Midbrain dopamine neurons have long been thought to collectively signal a value prediction error, indicating whether the value of an event is greater or less than expected.  A few years ago, our lab showed that these neurons also signal if an event is different than expected, without regard for value.  In this paper, we build on this prior result by showing in both rats and humans that dopamine neurons or midbrain BOLD voxels, as a group, signal which unexpected event has occurred…

Featured Paper of the Month – February 2020
Published in Nature Communications by Bonaventura, Jordi; Eldridge, Mark A G; Hu, Feng; Gomez, Juan L; Sanchez-Soto, Marta; Abramyan, Ara M; Lam, Sherry; Boehm, Matthew A; Ruiz, Christina; Farrell, Mitchell R; Moreno, Andrea; Faress, Islam Mustafa Galal; Andersen, Niels; Lin, John Y; Moaddel, Ruin; Morris, Patrick J; Shi, Lei; Sibley, David R; Mahler, Stephen V; Nabavi, Sadegh; Pomper, Martin G; Bonci, Antonello; Horti, Andrew G; Richmond, Barry J; Michaelides, Michael

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are a popular chemogenetic technology for manipulation of neuronal activity in uninstrumented awake animals with potential for human applications as well. The prototypical DREADD agonist clozapine N-oxide (CNO) lacks brain entry and converts to clozapine, making it difficult to apply in basic and translational applications…

Featured Paper of the Month – January 2020
Published in Neuropsychopharmacology by Baeg, Eunha; Jedema, Hank P; Bradberry, Charles W

Drug-associated cues can intrude upon thinking, making relapse more likely. A measure of how strongly cues engage cognitive resources is called attentional bias. This is reflected in slightly longer response times on trials on a stimulus response task when drug cues are present compared to non-drug cues. In both cases, the cue is an irrelevant distractor that should just be ignored. Attentional bias is clinically important, because, across individuals, it correlates with extent of current use, and risk of relapse among those attempting abstinence…

Featured Paper of the Month – December 2019
Published in European Journal of Neuroscience by Mongia, Smriti; Yamaguchi, Tsuyoshi; Liu, Bing; Zhang, Shiliang; Wang, Huiling; Morales, Marisela

Unraveling the mystery of the glutamate-dopamine connection
The ventral tegmental area (VTA) is a brain structure that participates in the rewarding effects of drug use, but the role of specific neurons within the VTA is unclear. Scientists at NIDA’s Intramural Research Program conducted a set of studies to better understand the function of glutamate neurons in this addiction-relevant brain region. Glutamate is an excitatory neurotransmitter that plays an important role in brain development, normal brain processes, and pathological conditions like addiction…

Featured Paper of the Month – November 2019
Published in PLoS One by Schiffino, Felipe L; Siemian, Justin N; Petrella, Michele; Laing, Brenton T; Sarsfield, Sarah; Borja, Cara B; Gajendiran, Anjali; Zuccoli, Maria Laura; Aponte, Yeka

Motivated states such as food-seeking and consumption are essential for survival. A brain region called the lateral hypothalamus (LH) plays a fundamental role in regulating feeding and reward-related behaviors, but the contributions of specific neuronal subpopulations in the LH have not been thoroughly characterized. Here we examine how lateral hypothalamic leptin receptor-expressing (LH^LEPR) neurons, a subset of GABAergic cells, regulate motivation in mice. We trained mice to lever-press for food pellets on a progressive ratio schedule, a model commonly used to assess motivation to obtain a reinforcer…

Featured Paper of the Month – October 2019
Published in The Journal of Neuroscience by Hsu, Li-Ming; Keeley, Robin J; Liang, Xia; Brynildsen, Julia K; Lu, Hanbing; Yang, Yihong; Stein, Elliot A

Smoking remains a major public health burden, with approximately 20% of the world’s population engaging in regular smoking. Given the high relapse rate among smokers who enter treatments programs, early identification of vulnerable individuals, before the conversion from casual experimentation to regular smoking and addiction, is an important milestone to understand, prevent and potentially minimize nicotine dependence. Using a rodent model of nicotine dependence, we developed a quantitative predictor of subsequent nicotine dependence severity using graph theory-based analyses of fMRI BOLD resting state data collected at baseline, prior to any drug experience…

Featured Paper of the Month – September 2019
Published in ACS Pharmacology & Translational Science by Bonifazi, Alessandro; Yano, Hideaki; Guerrero, Adrian M; Kumar, Vivek; Hoffman, Alexander F; Lupica, Carl R; Shi, Lei; Newman, Amy Hauck

The discovery of functionally biased and physiologically beneficial ligands directed toward G-protein coupled receptors (GPCRs) has provided the impetus to design dopamine D₂ receptor (D₂R) targeted molecules that may be therapeutically advantageous for the treatment of certain neuropsychiatric or basal ganglia related disorders. Here we describe the synthesis of a novel series of D₂R agonists linking the D₂R unbiased agonist sumanirole with privileged secondary molecular fragments. The resulting ligands demonstrate improved D₂R affinity and selectivity over sumanirole…

Featured Paper of the Month – August 2019
Published in Elife by Madangopal, Rajtarun; Tunstall, Brendan J; Komer, Lauren E; Weber, Sophia J; Hoots, Jennifer K; Lennon, Veronica A; Bossert, Jennifer M; Epstein, David H; Shaham, Yavin; Hope, Bruce T

In abstinent drug addicts, cues formerly associated with drug-taking experiences gain relapse-inducing potency (‘incubate‘) over time. Animal models of incubation may help develop treatments to prevent relapse, but these models have ubiquitously focused on the role of conditioned stimuli (CSs) signaling drug delivery. Discriminative stimuli (DSs) are unique in that they exert stimulus-control over both drug taking and drug seeking behavior and are difficult to extinguish. For this reason, incubation of the excitatory effects of DSs that signal drug availability, not yet examined in preclinical studies, could be relevant to relapse prevention…

Featured Paper of the Month – July 2019
Published in The Journal of Neuroscience by Golden, Sam A; Jin, Michelle; Heins, Conor; Venniro, Marco; Michaelides, Michael; Shaham, Yavin

Aggression is often comorbid with neuropsychiatric diseases, including drug addiction. One form, appetitive aggression, exhibits symptomatology that mimics that of drug addiction and is hypothesized to be due to dysregulation of addiction-related reward circuits. However, our mechanistic understanding of the circuitry modulating appetitive operant aggression is limited…