Featured Paper of the Month

Exogenous ghrelin administration increases alcohol self-administration and modulates brain functional activity in heavy-drinking alcohol-dependent individuals.

Featured Paper of the Month – March 2018
Published in Molecular Psychiatry by Farokhnia, M; Grodin, E N; Lee, M R; Oot, E N; Blackburn, A N; Stangl, B L; Schwandt, M L; Farinelli, L A; Momenan, R; Ramchandani, V A; Leggio, L

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”)…

Bidirectional Modulation of Intrinsic Excitability in Rat Prelimbic Cortex Neuronal Ensembles and Non-Ensembles after Operant Learning

Featured Paper of the Month – February 2018
Published in The Journal of Neuroscience by Whitaker, Leslie R; Warren, Brandon L; Venniro, Marco; Harte, Tyler C; McPherson, Kylie B; Beidel, Jennifer; Bossert, Jennifer M; Shaham, Yavin; Bonci, Antonello; Hope, Bruce T

Learned associations between environmental stimuli and rewards drive learning and motivated behavior. These memories are thought to be encoded by alterations within specific patterns of sparsely distributed neurons called neuronal ensembles that are selectively activated by reward-predictive stimuli. Here we use the Fos promoter to identify strongly activated neuronal ensembles in rat prelimbic cortex (PLC) and assess altered intrinsic excitability following 10 days of operant food self-administration training. First, we selectively ablated Fos-expressing PLC neurons that were active during food self-administration…

High fat diet disrupts endoplasmic reticulum calcium homeostasis in the rat liver.

Featured Paper of the Month – January 2018
Published in The Journal of Hepatology by Wires, Emily S; Trychta, Kathleen A; Back, Susanne; Sulima, Agnieszka; Rice, Kenner C; Harvey, Brandon K

From the NIDA IRP Molecular Mechanisms of Cellular Stress and Inflammation Section

The endoplasmic reticulum (ER) is cellular organelle that performs critical functions such as the production and processing of proteins, lipids and drugs. The ER also serves as the primary storage site for calcium inside the cell. Using a novel biological sensor protein called GLuc-SERCaMP developed by our laboratory at the NIDA IRP, we show that high fat diets causes changes to ER calcium in the livers of rats. Unrestricted access to high fat food pellets caused molecular changes to regulators of ER calcium and an increase in markers of fatty liver disease…

Deletion of Type 2 Metabotropic Glutamate Receptor Decreases Sensitivity to Cocaine Reward in Rats.

Featured Paper of the Month – December 2017
Published in Cell Reports by Yang, Hong-Ju; Zhang, Hai-Ying; Bi, Guo-Hua; He, Yi; Gao, Jun-Tao; Xi, Zheng-Xiong

The etiology and pathophysiology of drug addiction are still not well understood. In this research paper, we show that genetic deletion of mGluR2, a presynaptic glutamate autoreceptor, decreases sensitivity to cocaine reward that causes a compensatory increase in cocaine intake and a decrease in relapse to cocaine-seeking behavior in rats…

A relationship between the aldosterone-mineralocorticoid receptor pathway and alcohol drinking: preliminary translational findings across rats, monkeys and humans.

Featured Paper of the Month – November 2017
Published in Molecular Psychiatry by Aoun, E G; Jimenez, V A; Vendruscolo, L F; Walter, N A R; Barbier, E; Ferrulli, A; Haass-Koffler, C L; Darakjian, P; Lee, M R; Addolorato, G; Heilig, M; Hitzemann, R; Koob, G F; Grant, K A; Leggio, L

This paper describes three separate studies, conducted with non-human primates, rats, and humans, that investigated the potential contribution of the hormone aldosterone and its mineralocorticoid receptor to alcohol use disorder. Taken together, these findings suggest a relationship between excessive alcohol use, alcohol use disorder, and specific changes in the aldosterone/ mineralocorticoid receptor pathway marked by increased circulating aldosterone and decreased mineralocorticoid receptor gene expression in the amygdala…

Compulsive Addiction-like Aggressive Behavior in Mice.

Featured Paper of the Month – October 2017
Published in Biological Psychiatry by Golden, Sam A; Heins, Conor; Venniro, Marco; Caprioli, Daniele; Zhang, Michelle; Epstein, David H; Shaham, Yavin

Some people are highly motivated to seek aggressive encounters, and among those who have been incarcerated for such behavior, recidivism rates are high. These observations echo two core features of drug addiction: high motivation to seek addictive substances, despite adverse consequences, and high relapse rates. Here we used established rodent models of drug addiction to determine whether they would be sensitive to “addiction-like” features of aggression in CD-1 mice…

Salience and default mode network dysregulation in chronic cocaine users predict treatment outcome.

Featured Paper of the Month – September 2017
Published in Brain by Geng, Xiujuan; Hu, Yuzheng; Gu, Hong; Salmeron, Betty Jo; Adinoff, Bryon; Stein, Elliot A; Yang, Yihong

While chronic cocaine use is associated with abnormalities in both brain structure and function within and interactions between regions, previous studies have been limited to interrogating structure and function independently, and the detected neural differences have not been applied to independent samples to assess the clinical relevance of results…

The Novel Modafinil Analog, JJC8-016, as a Potential Cocaine Abuse Pharmacotherapeutic.

Featured Paper of the Month – August 2017
Published in Neuropsychopharmacology by Zhang, Hai-Ying; Bi, Guo-Hua; Yang, Hong-Ju; He, Yi; Xue, Gilbert; Cao, Jiajing; Tanda, Gianluigi; Gardner, Eliot L; Newman, Amy Hauck; Xi, Zheng-Xiong

(+/-)Modafinil ((+/-)MOD) and its R-enantiomer (R-modafinil; R-MOD) have been investigated for their potential as treatments for psychostimulant addiction. We recently reported a series of (+/-)MOD analogs, of which JJC8-016 (N-(2-((bis(4-fluorophenyl)methyl)thio)ethyl)-3-phenylpropan-1-amine) was selected for further development. JJC8-016 and R-MOD were evaluated for binding across ~70 receptors, transporters, and enzymes…

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

Featured Paper of the Month – July 2017
Published in The Journal of Medical Chemistry by Kumar, Vivek; Moritz, Amy E; Keck, Thomas M; Bonifazi, Alessandro; Ellenberger, Michael P; Sibley, Christopher D; Free, Benjamin R; Shi, Lei; Lane, Robert J; Sibley, David R; Newman, Amy Hauck

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…

Lateral Habenula Involvement in Impulsive Cocaine Seeking

Featured Paper of the Month – June 2017
Published in Neuropsychopharmacology by Zapata, Agustin; Hwang, Eun-Kyung; Lupica, Carl R

The lateral habenula (LHb) is a brain structure receiving inputs from limbic forebrain areas and innervating major midbrain monoaminergic nuclei. Evidence indicates LHb involvement 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…