Article
Biochemistry & Molecular Biology
Ross van de Wetering, Amy Ewald, Susan Welsh, Lindsay Kornberger, Samuel E. Williamson, Bryan D. McElroy, Eduardo R. Butelman, Thomas E. Prisinzano, Bronwyn M. Kivell
Summary: This preclinical study evaluated the G-protein-biased analogue of SalA, 16-BrSalA, for its anticocaine effects and side effects, and found that it has improved pharmacokinetic profiles and fewer side effects.
Article
Biochemistry & Molecular Biology
Qianhan Ma, Susan Wonnacott, Sarah J. Bailey, Christopher P. Bailey
Summary: Kappa opioid receptors (KOPr) play a role in the response to stress, and are associated with the treatment of stress-related psychiatric disorders. This study found that there are sex differences in the activation of brain regions in male and female mice following an acute stressor or a KOPr agonist. These differences may contribute to sex differences in stress-related psychiatric disorders and the treatment of depression, anxiety, and addiction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Gabrielle C. Gregoriou, Sahil D. Patel, Sebastian Pyne, Bryony L. Winters, Elena E. Bagley
Summary: Opioid withdrawal disrupts emotional learning circuits, leading to relapse and compulsive drug use. This study reveals that during withdrawal, protein kinase A (PKA) activation reduces the inhibitory effect of endogenous opioids on synaptic transmission in the amygdala, shifting the excitatory/inhibitory balance and contributing to relapse. Restoring endogenous peptide activity during withdrawal may mitigate these disruptions and prevent relapse behaviors.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Cell Biology
Wei Wang, Xueyi Xie, Xiaowen Zhuang, Yufei Huang, Tao Tan, Himanshu Gangal, Zhenbo Huang, William Purvines, Xuehua Wang, Alexander Stefanov, Ruifeng Chen, Lucas Rodriggs, Anita Chaiprasert, Emily Yu, Valerie Vierkant, Michelle Hook, Yun Huang, Emmanuel Darcq, Jun Wang
Summary: Withdrawal from chronic opioid use leads to hypodopaminergic states and negative affect, promoting relapse. Activation of MORs in dMSNs in the striatal patch compartment suppresses striatopallidal transmission, and withdrawal potentiated this transmission. Fentanyl self-administration enhances striatonigral transmission and reduces dopaminergic activity, while activated striatal neurons mediate contextual memory retrieval. Inhibition of striatal MOR+ neurons rescues fentanyl withdrawal-induced physical symptoms and anxiety-like behaviors. These findings suggest that chronic opioid use induces GABAergic striatopallidal and striatonigral plasticity, leading to hypodopaminergic states and relapse.
Article
Neurosciences
Volker Neugebauer, Peyton Presto, Vadim Yakhnitsa, Nico Antenucci, Brianna Mendoza, Guangchen Ji
Summary: Neuroplasticity in cortico-limbic circuits is important in pain persistence and modulation. The amygdala plays a key role in the emotional dimension of pain, and interactions with prefrontal cortical regions change in pain conditions. Other regions in the limbic system are also involved in pain modulation. The corticolimbic system contains opioids and opioid receptors, and their modulatory effects and potential opposing functions are still not fully understood.
Article
Clinical Neurology
Marsida Kallupi, Jenni Kononoff, Philippe A. Melas, Johanna S. Qvist, Giordano de Guglielmo, Eric R. Kandel, Olivier George
Summary: The study found that DBS of the NAcc shell did not decrease cocaine intake, but had therapeutic effects on reducing negative emotional states during withdrawal.
Review
Neurosciences
Aaron Limoges, Hector E. Yarur, Hugo A. Tejeda
Summary: This article reviews the role of the Dyn/KOR system in regulating amygdala circuitry and its implications in emotional and stress-related behaviors. The study highlights the need for future research to further understand the impact of the Dyn/KOR system on amygdala-related behaviors and suggests that targeting this system could offer novel approaches for treating neuropsychiatric disorders.
FRONTIERS IN SYSTEMS NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Joakim W. Ronstroem, Natalie L. Johnson, Stephen T. Jones, Sara J. Werner, Hillary A. Wadsworth, James N. Brundage, Valerie Stolp, Nicholas M. Graziane, Yuval Silberman, Scott C. Steffensen, Jordan T. Yorgason
Summary: Opioid use and withdrawal can lead to behavioral adaptations, such as drug seeking and anxiety. The basolateral amygdala (BLA) controls these behaviors through the activation of principal neurons. The study found that lateral paracapsular (LPC) GABAergic inhibitory neurons, which express mu-opioid receptors (MORs), are potential targets in opioid-use disorders and anxiety-like behaviors. The research also demonstrated that repeated opioid exposure impairs the excitability of LPC neurons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Gary B. Kaplan, Benjamin L. Thompson
Summary: Opioid use disorder is characterized by excessive use of opioids, inability to control use, withdrawal syndrome, and likelihood of relapse. The opponent process view of motivation suggests that opioid addiction involves positive affective experiences during active involvement and negative affective experiences during abstinence. These negative experiences are hypothesized to be caused by neuroadaptations in the extended amygdala, which includes the CeA, BNST, and NAc shell, as well as input from the BLA. Animal models of opioid withdrawal demonstrate the somatic, motivational, affective, and learning related aspects of withdrawal. Neuroadaptations in the extended amygdala lead to aversive and fear-related effects, hypodopaminergia, and increased vulnerability to relapse. Understanding and reversing these neuroadaptations could lead to new interventions for opioid use disorder.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Paul M. Burkat
Summary: This study utilized PK and PD modeling to examine the mechanisms of anxiety treatment and addiction of alprazolam. The results showed that the brain concentration of alprazolam corresponded to changes in beta rhythm activity, peak saccade velocity, mood improvement, cognitive speed slowing, and digit symbol substitution test scores. The PD models suggested that the maximal effects of alprazolam on cognitive slowing, cognitive impairment, sedation, and mood improvement occur sequentially following the brain concentration-time profile.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Yuma T. Ortiz, Lance R. McMahon, Jenny L. Wilkerson
Summary: Cannabinoids, including THC and CBD, hold promise as therapeutics for various health issues, but conclusive evidence supporting their use in most central nervous system indications is still lacking. Clinical studies mostly focus on purified THC and CBD, while few studies examine whole plant cannabis products.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Neurosciences
Marianne L. Seney, Sam-Moon Kim, Jill R. Glausier, Mariah A. Hildebrand, Xiangning Xue, Wei Zong, Jiebiao Wang, Micah A. Shelton, BaDoi N. Phan, Chaitanya Srinivasan, Andreas R. Pfenning, George C. Tseng, David A. Lewis, Zachary Freyberg, Ryan W. Logan
Summary: The study utilized RNA sequencing to analyze brain regions in subjects with OUD, identifying gene transcription related to synaptic remodeling and neuroinflammation. Microglia were implicated as a potential driver for opioid-induced neuroplasticity, with genetic liabilities for risky behavior, ADHD, and depression found in individuals with OUD.
BIOLOGICAL PSYCHIATRY
(2021)
Article
Neurosciences
Matthew Hein, Guangchen Ji, Dalton Tidwell, Preston D'Souza, Takaki Kiritoshi, Vadim Yakhnitsa, Edita Navratilova, Frank Porreca, Volker Neugebauer
Summary: The activation of KOR in the CeA increases activity of amygdala CRF neurons through synaptic disinhibition, leading to averse-affective pain-like behaviors.
Article
Biology
Marcus M. Weera, Abigail E. Agoglia, Eliza Douglass, Zhiying Jiang, Shivakumar Rajamanickam, Rosetta S. Shackett, Melissa A. Herman, Nicholas J. Justice, Nicholas W. Gilpin
Summary: We have successfully generated and validated a transgenic CRF1-Cre-(td)Tomato rat model, which can be used to study the role of CRF1 receptor-expressing neurons in hormone-mediated behaviors. We found that the expression pattern of this rat model is similar to the known expression pattern of CRF1 cells, and it can be investigated using modern genetic techniques.
Article
Neurosciences
Madison A. Baird, TingTing Y. Hsu, Rachel Wang, Barbara Juarez, Larry S. Zweifel
Summary: Genetic inactivation of the K opioid receptor encoding gene Oprk1 in the central nucleus of the amygdala (CeA) results in increased anxiety-like behavior and impaired conditioned threat discrimination, while inactivation of the dynorphin encoding gene Pdyn in the CeA has no effect on anxiety or conditioned threat discrimination. However, inactivation of Pdyn from multiple sources, intrinsic and extrinsic to the CeA, phenocopies Oprk1 inactivation. These findings suggest that dynorphin inputs to the CeA signal through KOR to promote threat discrimination and dampen anxiety.
Article
Clinical Neurology
Marsida Kallupi, Jenni Kononoff, Philippe A. Melas, Johanna S. Qvist, Giordano de Guglielmo, Eric R. Kandel, Olivier George
Summary: The study found that DBS of the NAcc shell did not decrease cocaine intake, but had therapeutic effects on reducing negative emotional states during withdrawal.
Article
Neurosciences
Taryn E. Grieder, Mandy Yee, Hector Vargas-Perez, Geith Maal-Bared, Susan George, Ryan Ting-A-Kee, Olivier George, Derek van der Kooy
Summary: Brain-derived neurotrophic factor (BDNF) plays a crucial role in the transition from a non-dependent motivational state to a drug-dependent and drug-withdrawn motivational state. Chronic nicotine increases BDNF in the rodent brain and is associated with smoking severity in humans. The signaling of BDNF in the ventral tegmental area (VTA) is identified as a critical neurobiological substrate for the transition to nicotine dependence.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2022)
Review
Neurosciences
Sierra Simpson, Rio Mclellan, Emma Wellmeyer, Frederic Matalon, Olivier George
Summary: Substance use disorders (SUDs) pose a significant public health crisis, accounting for 5.4% of the global disease burden. The gut microbiome has been linked to SUDs and related conditions such as anxiety, depression, pain, and stress. Understanding the mechanisms influencing behavioral changes and drug use is crucial in developing novel treatments for SUDs.
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
(2022)
Editorial Material
Neurosciences
Alicia J. Avelar, Olivier George
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Behavioral Sciences
Michael T. Bowen, Olivier George, Dawn E. Muskiewicz, F. Scott Hall
Summary: Understanding the factors that contribute to the escalation of alcohol consumption is crucial for understanding the transition from non/social drinking to AUD and improving treatment. This review discusses how the way ethanol is consumed, as well as individual and environmental factors, contribute to the escalation of ethanol consumption. Additionally, the review examines how these factors are modeled in animals.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2022)
Article
Neurosciences
Kokila Shankar, Frederic Ambroggi, Olivier George
Summary: The study aimed to investigate the effects of acute nicotine intake on feeding and drinking behavior. Microstructural and macrostructural behavioral analyses were employed to examine changes in food and water intake at different timescales.
PSYCHOPHARMACOLOGY
(2022)
Article
Behavioral Sciences
Lieselot L. G. Carrette, Cristina Corral, Brent Boomhower, Molly Brennan, Caitlin Crook, Clara Ortez, Kokila Shankar, Sierra Simpson, Lisa Maturin, Leah C. Solberg Woods, Abraham A. Palmer, Giordano de Guglielmo, Olivier George
Summary: High blood leptin levels may serve as a protective factor against the development of cocaine addiction-like behavior, and exogenous leptin reduces the motivation to take and seek cocaine. However, changes in bodyweight and blood leptin levels are not relevant biomarkers for addiction-like behaviors.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2022)
Article
Neurosciences
Sascha H. Duttke, Patricia Montilla-Perez, Max W. Chang, Hairi Li, Hao Chen, Lieselot L. G. Carrette, Giordano de Guglielmo, Olivier George, Abraham A. Palmer, Christopher Benner, Francesca Telese
Summary: Substance abuse and addiction have significant impacts on healthcare, the economy, and the workforce. Understanding the gene regulatory mechanisms underlying addiction is crucial for effective treatments. This study used advanced transcriptomics methods to explore how drug exposure alters gene regulatory networks in the brain. The findings highlight the disruption of gene regulatory programs by addiction and the potential role of glial cells in driving addiction-related phenotypes.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Neurosciences
Giordano de Guglielmo, Sierra Simpson, Adam Kimbrough, Dana Conlisk, Robert Baker, Maxwell Cantor, Marsida Kallupi, Olivier George
Summary: The most widely used animal models of alcohol dependence have limitations due to forced exposure to ethanol. A novel animal model of voluntary induction of alcohol dependence using ethanol vapor self-administration (EVSA) has been developed. However, it is unclear whether EVSA leads to an escalation of alcohol drinking and associated neuroadaptations in brain regions related to stress, reward, and habit. This study compares the levels of alcohol drinking and measures the number of Fos+ neurons in key brain regions during acute withdrawal, revealing differences between the EVSA and passive models.
Editorial Material
Neurosciences
Olivier George, Serge H. Ahmed, Nicholas W. Gilpin
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Vidhya Kumaresan, Yolpanhchana Lim, Poorva Juneja, Allison E. Tipton, Giordano de Guglielmo, Lieselot L. G. Carrette, Marsida Kallupi, Lisa Maturin, Ying Liu, Olivier George, Huiping Zhang
Summary: Cocaine administration alters miRNA expression in the cortico-accumbal pathway, potentially impacting gene expression regulation during withdrawal. This study examined miRNA changes in this pathway during acute withdrawal and protracted abstinence from escalated cocaine intake. Results showed differential miRNA expression and pathways enriched in mRNA targets associated with addiction. The findings emphasize the importance of miRNA expression in addiction-related circuits and suggest the potential for developing biomarkers and therapies targeting abstinence-associated miRNAs.
Correction
Neurosciences
Jessica L. Zhou, Giordano de Guglielmo, Aaron J. Ho, Marsida Kallupi, Narayan Pokhrel, Hai-Ri Li, Apurva S. Chitre, Daniel Munro, Pejman Mohammadi, Lieselot L. G. Carrette, Olivier George, Abraham A. Palmer, Graham Mcvicker, Francesca Telese
NATURE NEUROSCIENCE
(2023)
Article
Neurosciences
Marsida Kallupi, Roberto Ciccocioppo
Summary: Environmental conditioning factors have a significant impact on alcohol-seeking behavior and the maintenance of alcohol use in individuals with alcohol dependence. This study investigates the correlation between the reward magnitude of the primary reinforcer and the reinstatement evoked by cues predictive of their availability in male rats. The results demonstrate a dissociation between the rewarding magnitude of the primary reinforcer and its ability to trigger relapse upon presentation of a cue previously associated with it. Additionally, the mGluR5 system plays a significant role in regulating alcohol-seeking behavior.
Meeting Abstract
Neurosciences
Jessica Zhou, Giordano de Guglielmo, Aaron Ho, Marsida Kallupi, Hairi Li, Lieselot Carrette, Olivier George, Abraham Palmer, Graham McVicker, Francesca Telese
NEUROPSYCHOPHARMACOLOGY
(2022)
Review
Neurosciences
Maya Jammoul, Dareen Jammoul, Kevin K. Wang, Firas Kobeissy, Ralph G. Depalma
Summary: This article reviews the possible mechanisms by which traumatic brain injury (TBI) may stimulate the development of opioid use disorder (OUD) and discusses the interaction between these two processes. CNS damage due to TBI appears to drive adverse effects of subsequent OUD, with pain being a risk factor for opioid use after TBI.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Danusa Mar Arcego, Jan-Paul Buschdorf, Nicholas O'Toole, Zihan Wang, Barbara Barth, Irina Pokhvisneva, Nirmala Arul Rayan, Sachin Patel, Euclides Jose de Mendonca Filho, Patrick Lee, Jennifer Tan, Ming Xuan Koh, Chu Ming Sim, Carine Parent, Randriely Merscher Sobreira de Lima, Andrew Clappison, Kieran J. O'Donnell, Carla Dalmaz, Janine Arloth, Nadine Provencal, Elisabeth B. Binder, Josie Diorio, Patricia Pelufo Silveira, Michael J. Meaney
Summary: This study investigates the impact of environmental influences on mental health by integrating transcriptomic data from animal models with human data. The results suggest that hippocampal glucocorticoid-related transcriptional activity mediates the effects of early adversity on neural mechanisms implicated in psychiatric disorders.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Milenna T. van Dijk, Ardesheer Talati, Pratik Kashyap, Karan Desai, Nora C. Kelsall, Marc J. Gameroff, Natalie Aw, Eyal Abraham, Breda Cullen, Jiook Cha, Christoph Anacker, Myrna M. Weissman, Jonathan Posner
Summary: This study found that maternal stress is associated with future depressive symptoms and alterations in microstructure of the dentate gyrus (DG) in offspring. These results were consistent across two independent cohorts.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Josephine C. McGowan, Liliana R. Ladner, Claire X. Shubeck, Juliana Tapia, Christina T. LaGamma, Amanda Anqueira-Gonzalez, Ariana DeFrancesco, Briana K. Chen, Holly C. Hunsberger, Ezra J. Sydnor, Ryan W. Logan, Tzong-Shiue Yu, Steven G. Kernie, Christine A. Denny
Summary: Traumatic brain injury (TBI) leads to fear generalization by altering fear memory traces, and this symptom can be improved with (R,S)-ketamine.
BIOLOGICAL PSYCHIATRY
(2024)