Featured Paper of the Month

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…

Featured Paper of the Month – June 2019
Published in Biological Psychiatry by Nicolas, Celine; Russell, Trinity I; Pierce, Anne F; Maldera, Steeve; Holley, Amanda; You, Zhi-Bing; McCarthy, Margaret M; Shaham, Yavin; Ikemoto, Satoshi

We examined whether binge cocaine intake has an impact on drug craving after abstinence and whether it has differential effects between male and female rats. We used an intermittent access cocaine self-administration to mimic binge intake and compare it with a continuous access self-administration. The intermittent access procedure caused stronger cocaine craving following abstinence than the continuous access procedure, and this effect was greater in female than male rats…

Featured Paper of the Month – May 2019
Published in Neuron by Takahashi, Yuji K; Stalnaker, Thomas A; Marrero-Garcia, Yasmin; Rada, Ray M; Schoenbaum, Geoffrey

Addiction is a disorder of behavioral control and learning. While this may reflect pre-existing propensities, drug use also clearly contributes by causing changes in outcome processing in prefrontal and striatal regions. This altered processing is associated with behavioral deficits, including changes in learning. These areas provide critical input to midbrain dopamine neurons regarding expected outcomes, suggesting that effects on learning may result from changes in dopaminergic error signaling…

Featured Paper of the Month – April 2019
Published in Neuropsychopharmacology by You, Zhi-Bing; Bi, Guo-Hua; Galaj, Ewa; Kumar, Vivek; Cao, Jianjing; Gadiano, Alexandra; Rais, Rana; Slusher, Barbara S; Gardner, Eliot L; Xi, Zheng-Xiong; Newman, Amy Hauck

Opioid use disorders are currently a serious health problem worldwide and yet prescription opioids remain as the most effective medications to treat pain. VK4-116, a highly selective dopamine D3 receptor antagonist, significantly inhibited acquisition of oxycodone self-administration behaviors and decreased oxycodone seeking in several rodent models. VK4-116 was also effective in a model of opioid-induced relapse and on diminishing the aversive effects of naloxone precipitated withdrawal…

Featured Paper of the Month – March 2019
Published in Molecular Neurobiology by Blackwood, Christopher A; Hoerle, Reece; Leary, Michael; Schroeder, Jennifer; Job, Martin O; McCoy, Michael T; Ladenheim, Bruce; Jayanthi, Subramaniam; Cadet, Jean Lud

Abuse of opioids including oxycodone is very prevalent in the US. Researchers in the laboratory of Jean Lud Cadet in the NIDA IRP have shown that when rats are given access to oxycodone for several hours, some of the rats will increase the amount of the drug in a very steep fashion whereas others will only take moderate quantities of the drug. They also found, however, that, after a month of withdrawal from oxycodone, all those rats had decreased levels of mu opioid receptor protein in the dorsal striatum, a brain region that is important for habit forming…

Featured Paper of the Month – February 2019
Published in Neuropsychopharmacology by Gao, Jun-Tao; Jordan, Chloe J; Bi, Guo-Hua; He, Yi; Yang, Hong-Ju; Gardner, Eliot L; Xi, Zheng-Xiong

Despite extensive research in the past decades, little is known about the etiology of opioid addiction. In this study, Xi and colleagues found that genetic deletion of mGluR2, a glutamate receptor subtype, in rats caused an increase in brain dopamine responses to heroin and in opioid reward, facilitating the development of opioid use and abuse. This finding suggests that low-mGluR2 expression in the brain may be a risk factor for the development of opioid abuse and addiction…