Featured Paper of the Month

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…

Featured Paper of the Month – January 2019
Published in Journal of the American Society for Mass Spectrometry by Jackson, Shelley N; Muller, Ludovic; Roux, Aurelie; Oktem, Berk; Moskovets, Eugene; Doroshenko, Vladimir M; Woods, Amina S

Gangliosides are complex glycosphingolipids and have been implicated in brain development, neuritogenesis, memory formation, synaptic transmission and aging. Disruptions in ganglioside metabolism has been linked to several diseases such as Niemann-Pick C, and Gaucher disease types II, Alzheimer disease and Guillain-Barre syndrome. GD1s are the most abundant ganglioside species in the mammalian brain and consist of two structural isomers, GD1a and GD1b.Traditionally, the only way to analyze these isomers by mass spectrometry involved  extraction and thus the researcher loses information about the location of the isomers in tissue…

Featured Paper of the Month – December 2018
Published in Neuropsychopharmacology by Xin, Wendy; Schuebel, Kornel E; Jair, Kam-Wing; Cimbro, Raffaello; Biase, Lindsay M De; Goldman, David; Bonci, Antonello

Astrocytes are ubiquitous CNS cells that support tissue homeostasis through ion buffering, neurotransmitter recycling, and regulation of CNS vasculature. Yet, despite the essential functional roles they fill, very little is known about the physiology of astrocytes in the ventral midbrain, a region that houses dopamine-releasing neurons and is critical for reward learning and motivated behaviors. Using a combination of whole-transcriptome sequencing, histology, slice electrophysiology, and calcium imaging, Xin et al. performed the first functional and molecular profiling of ventral midbrain astrocytes and observed numerous differences between these cells and their telencephalic counterparts, both in their gene expression profile and in their physiological properties…

Featured Paper of the Month – Novermber 2018
Published in Cell Reports by Root, David H; Zhang, Shiliang; Barker, David J; Miranda-Barrientos, Jorge; Liu, Bing; Wang, Hui-Ling; Morales, Marisela

Root and Zhang et al. (from Dr. Morales’ lab) identified throughout the brain concentrated populations of glutamate and GABA co-transmitting neurons in ventral tegmental area, entopeduncular, and supramammillary nuclei. Single axon terminals from these neurons form a common synaptic architecture that co-transmit glutamate and GABA from distinct synaptic vesicles at independent asymmetric or symmetric synapses…

Featured Paper of the Month – October 2018
Published in Molecular Psychiatry by Lee, Mary R; Tapocik, Jenica D; Ghareeb, Mwlod; Schwandt, Melanie L; Dias, Alexandra A; Le, April N; Cobbina, Enoch; Farinelli, Lisa A; Bouhlal, Sofia; Farokhnia, Mehdi; Heilig, Markus; Akhlaghi, Fatemeh; Leggio, Lorenzo

Understanding the neurobiological substrates of excessive alcohol consumption may substantially facilitate efforts to develop better treatments. The cross-talk between the gastrointestinal and central nervous systems, often referred to as the gut–brain axis, is a promising yet underexplored domain in this regard.  Ghrelin is a hormone primarily produced by the stomach and known for its role in increasing appetite and food intake (the “hunger hormone”). Recent animal and human studies suggest that ghrelin may also be involved in alcohol-seeking behaviors.  In rodent experiments, blocking the ghrelin receptor suppresses alcohol seeking and consumption…

Featured Paper of the Month – September 2018
Published in Neuropsychopharmacology by Torres, Oscar V; Jayanthi, Subramaniam; McCoy, Michael T; Cadet, Jean Lud

Methamphetamine addiction is a public health threat throughout the world. Investigators in Dr. Cadet’s laboratory in the intramural program have developed a rat model of methamphetamine addiction that includes one of the psychiatric criteria used to make that diagnosis in humans. In that model, they used footshocks to represent adverse consequences that are present during the clinical course of addiction. Contingent footshocks helped the investigators to identify some rats (addicted) that continue to press a lever to get methamphetamine whereas other rats (non-addicted) suppress or stop their taking of methamphetamine in the presence of these adverse consequences…

Featured Paper of the Month – August 2018
Published in The Journal of Neuroscience by Li, Xuan; Witonsky, Kailyn R; Lofaro, Olivia M; Surjono, Felicia; Zhang, Jianjun; Bossert, Jennifer M; Shaham, Yavin

Methamphetamine seeking progressively increases after withdrawal from drug self-administration, a phenomenon termed incubation of methamphetamine craving. We previously found that D1R-mediated dopamine transmission in dorsomedial striatum plays a critical role in this incubation phenomenon. Here, we used neuroanatomical and neuropharmacological methods in rats to demonstrate that an interaction between the glutamatergic projection from the lateral anterior intralaminar nuclei of thalamus to dorsomedial striatum and local dopamine D1Rs plays a critical role in relapse to methamphetamine seeking after prolonged withdrawal…