Featured Paper of the Month

The novel ghrelin receptor inverse agonist PF-5190457 administered with alcohol: preclinical safety experiments and a phase 1b human laboratory study.

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…

Selective Activation of Striatal NGF-TrkA/p75NTR/ MAPK Intracellular Signaling in Rats That Show Suppression of Methamphetamine Intake 30 Days following Drug Abstinence

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…

Role of Anterior Intralaminar Nuclei of Thalamus Projections to Dorsomedial Striatum in Incubation of Methamphetamine Craving.

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…

Orbitofrontal neurons signal sensory associations underlying model-based inference in a sensory preconditioning task.

Featured Paper of the Month – July 2018
Published in Elife by Sadacca, Brian F; Wied, Heather M; Lopatina, Nina; Saini, Gurpreet K; Nemirovsky, Daniel; Schoenbaum, Geoffrey

Using knowledge of the structure of the world to infer value is at the heart of model-based reasoning and relies on a circuit that includes the orbitofrontal cortex (OFC). Some accounts link this to the representation of biological significance or value by neurons in OFC, while other models focus on the representation of associative structure or cognitive maps. Here we tested between these accounts by recording OFC neurons in rats during an OFC-dependent sensory preconditioning task…

Delta Rhythm Orchestrates the Neural Activity Underlying the Resting State BOLD Signal via Phase–amplitude Coupling.

Featured Paper of the Month – June 2018
Published in Cerebral Cortex by Jaime, Saul; Gu, Hong; Sadacca, Brian F; Stein, Elliot A; Cavazos, Jose E; Yang, Yihong; Lu, Hanbing

Our brains always work, consciously or unconsciously. Functional connectivity MRI has identified so-called resting state brain networks (e.g. default mode network). Aberrant activity in such networks is implicated in neurological and psychiatric disorders. This work applies simultaneous electrophysiological recording and functional MRI to investigate the neurophysiological basis of the network activity…

Fentanyl-Induced Brain Hypoxia Triggers Brain Hyperglycemia and Biphasic Changes in Brain Temperature.

Featured Paper of the Month – May 2018
Published in Neuropsychopharmacology by Solis, Ernesto Jr; Cameron-Burr, Keaton T; Shaham, Yavin; Kiyatkin, Eugene A

Fentanyl is a potent synthetic opioid used clinically to treat pain and as a general anesthetic. Recently, fentanyl has emerged as a recreational drug and its overdose has been linked to numerous deaths in the US. To better understand how fentanyl affects the brain, we used electrochemical techniques in rats and examined the effect of intravenous fentanyl on oxygen and glucose levels in the nucleus accumbens, a brain region implicated in reward and addiction…

Lateral Preoptic Control of the Lateral Habenula through Convergent Glutamate and GABA Transmission.

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

The lateral habenula (LHb) is a brain structure that participates in cognitive and emotional processing and has been implicated in several mental disorders. Although one of the largest inputs to the LHb originates in the lateral preoptic area (LPO), little is known about how the LPO participates in the regulation of LHb function. In their recent study, Barker and colleagues provide evidence that the LPO exerts bivalent control over the LHb through the convergent transmission of excitatory LPO glutamate and inhibitory LPO g-aminobutyric acid (GABA) onto single LHb neurons…

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

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…