Article
Neurosciences
Dillon J. McGovern, Abigail M. Polter, Emily D. Prevost, Annie Ly, Connor J. McNulty, Bodhi Rubinstein, David H. Root
Summary: A three-neuron model of VTA opioid function has been discovered, involving a mu-opioid receptor gated VTA glutamate neuron pathway to VTA dopamine neurons. These glutamate-Mu opioid receptor neurons are distributed in the anterior VTA, while the majority of VTA mu-opioid receptor neurons are GABAergic neurons in the posterior VTA. Optogenetic stimulation of VTA glutamate neurons can induce excitatory currents in VTA dopamine neurons, regulated by the mu-opioid receptor.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Elizabeth N. Holly, M. Felicia Davatolhagh, Rodrigo A. Espana, Marc Fuccillo
Summary: The dorsomedial striatum plays a central role in supporting goal-directed learning and motor performance, with local inhibitory GABAergic networks modulating striatal output and behavior. The sparse low-threshold spiking interneuron subtype is involved in regulating initial goal-directed learning, while striatal dopamine signaling is essential for reward-related neuromodulation and motor behaviors.
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
Carlee Toddes, Emilia M. Lefevre, Dieter D. Brandner, Lauryn Zugschwert, Patrick E. Rothwell
Summary: The study focused on the impact of partial reduction of mu-opioid receptor signaling on nucleus accumbens microcircuitry and social behavior, revealing increased inhibitory synaptic transmission in male mutants but not in female mutants. These changes were more pronounced in Oprm1(+/-) mutants and resulted in altered social behavior, as well as social deficits in conditioned place preference and reciprocal social interaction. Additionally, interacting with Oprm1 mutants affected the social behavior of wild-type test partners, indicating a role for mu-opioid signaling dysregulation in social deficits associated with neuropsychiatric conditions.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Neurosciences
Lisa Z. Fang, Meaghan C. Creed
Summary: This article provides an overview of the neurochemical and molecular diversity of striatal and pallidal neurons, as well as recent studies on circuit connectivity in rodents. The authors highlight the anatomical organizational principles of the dorsal and ventral basal ganglia pathways. Future research integrating the molecular and anatomical properties of specific subpopulations may help resolve controversies related to the function of basal ganglia networks.
NATURE NEUROSCIENCE
(2023)
Article
Neurosciences
Nycole Maza, Dandan Wang, Cody Kowalski, Hannah M. Stoveken, Maria Dao, Omar K. Sial, Andrew C. Giles, Brock Grill, Kirill A. Martemyanov
Summary: Repeated exposure to opioids leads to the development of tolerance, limiting their analgesic effects and increasing the risk of abuse and overdose. This study identified Ptchd1 as a gene involved in regulating opioid tolerance through its effects on receptor trafficking and desensitization. The findings suggest an evolutionarily conserved role for Ptchd1 in protecting against opioid overstimulation.
NATURE NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Tao Che, Bryan L. Roth
Summary: This article explores the molecular basis of opioid receptor signaling, including the binding of opioids to receptors and the molecular determinants of signaling pathways. Additionally, the synergy between computational biology and medicinal chemistry is mentioned as a means to expedite the discovery of more effective and safer opioid compounds.
Article
Multidisciplinary Sciences
Debora Masini, Ole Kiehn
Summary: The study demonstrates that cell-type specific stimulation of brainstem neurons can restore severe locomotor deficit in mouse models of parkinsonism, suggesting a potential target for neuromodulatory restoration of locomotor function in Parkinson's disease.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Korleki Akiti, Iku Tsutsui-Kimura, Yudi Xie, Alexander Mathis, Jeffrey E. Markowitz, Rockwell Anyoha, Sandeep Robert Datta, Mackenzie Weygandt Mathis, Naoshige Uchida, Mitsuko Watabe-Uchida
Summary: In this study, the behavior of mice freely interacting with a novel object was characterized using multi-point tracking and behavioral segmentation techniques. The results revealed that novelty elicits a characteristic sequence of behavior, and dopamine in the tail of the striatum suppresses object engagement. A reinforcement-learning model explained the behavioral dynamics and individual variability, uncovering an algorithmic similarity between reward- and threat-related dopamine sub-systems.
Review
Endocrinology & Metabolism
Nikolai Jaschke, Sophie Paehlig, Ying-Xian Pan, Lorenz C. Hofbauer, Andy Goebel, Tilman D. Rachner
Summary: This review focuses on the origin, molecular biology, and physiology of endogenous opioids, particularly the mu-opioid receptor networks within the endocrine system. The involvement of these networks in regulating distinct endocrine functions is supported by current evidence. The review provides an integrated perspective on mu-opioid receptor biology and offers insights into future studies and unresolved questions in this field.
TRENDS IN ENDOCRINOLOGY AND METABOLISM
(2021)
Article
Behavioral Sciences
Melissa Burns-Cusato, Joshua Rieskamp, Madeleine Nagy, Arpit Rana, William Hawkins, Sierra Panting
Summary: The incubation of eggs in avian species is thought to be reinforced by an opiate system, as evidenced by experiments with ring neck doves. Blocking opiate receptors with naloxone reduced time spent on the nest, while activating opiate receptors with morphine also decreased nest sitting time. These results suggest that the opiate system may play a previously unrecognized role in facilitating incubation behavior.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Soichiro Ide, Noriaki Iwase, Kenichi Arai, Masahiro Kojima, Shigeru Ushiyama, Kaori Taniko, Kazutaka Ikeda
Summary: Despite the widespread use of opioids for pain management, opioid addiction and the overdose crisis are becoming increasingly serious. A new nonpeptide ligand, UD-030, has been found to be a selective mu-opioid receptor antagonist and shows promise as a treatment option for opioid use disorder, with different characteristics from traditional medications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Xiaohui Bai, Kun Zhang, Chaopeng Ou, Yanyu Mu, Dongmei Chi, Jianxing Zhang, Jingxiu Huang, Xile Li, Yingjun Zhang, Wan Huang, Handong Ouyang
Summary: This study found that the expression of AKAP150 in the NAc is upregulated during morphine withdrawal, and inhibiting AKAP150 has a positive effect on alleviating withdrawal symptoms and improving test performance. AKAP150 in NAc D1R-MSNs is related to the performance of morphine withdrawal tests, while AKAP150 in NAc D2R-MSNs is relevant to the severity of physical responses.
Article
Pharmacology & Pharmacy
Paulo A. De Oliveira, Estefania Moreno, Nil Casajuana-Martin, Veronica Casado-Anguera, Ning-Sheng Cai, Gisela Andrea Camacho-Hernandez, Hu Zhu, Alessandro Bonifazi, Matthew D. Hall, David Weinshenker, Amy Hauck Newman, Diomedes E. Logothetis, Vicent Casado, Leigh D. Plant, Leonardo Pardo, Sergi Ferre
Summary: Recent studies suggest that the heteromers of mu-opioid receptors (MORs) and galanin Gal(1) receptors (Gal(1)Rs) in the mesencephalon play a role in mediating the dopaminergic effects of opioids. This study provides evidence for a predominant homodimeric structure of MOR and Gal(1)R when expressed individually and for their preference to form functional heterotetramers when co-expressed. The results show that this heteromerization leads to a change in G-protein coupling, providing a framework for Gs-Gi antagonist interaction.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Psychiatry
Serenella Tolomeo, Alex Baldacchino, Nora D. Volkow, J. Douglas Steele
Summary: Opioid use disorder has a significant impact globally, with limited recovery observed during protracted abstinence. Neuroimaging findings from this study support the allostasis theory by demonstrating improved negative valence brain function and similar positive valence function during protracted abstinence among patients.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Behavioral Sciences
N. Mittal, S. M. Fleming, A. Martinez, N. Thakore, R. L. Bell, W. T. Maddox, T. Schallert, C. L. Duvauchelle
BEHAVIOURAL BRAIN RESEARCH
(2020)
Review
Behavioral Sciences
Udita Datta, Sarah E. Schoenrock, Jason A. Bubier, Molly A. Bogue, James D. Jentsch, Ryan W. Logan, Lisa M. Tarantino, Elissa J. Chesler
GENES BRAIN AND BEHAVIOR
(2020)
Article
Neurosciences
Zachary T. Pennington, Jeremy M. Trott, Abha K. Rajbhandari, Kevin Li, Wendy M. Walwyn, Christopher J. Evans, Michael S. Fanselow
NEUROPSYCHOPHARMACOLOGY
(2020)
Article
Neurosciences
Sarah A. Schoenrock, Padam Kumar, Alexander Gomez-A, Price E. Dickson, Sam-Moon Kim, Lauren Bailey, Sofia Neira, Kyle D. Riker, Joseph Farrington, Christiann H. Gaines, Saad Khan, Troy D. Wilcox, Tyler A. Roy, Michael R. Leonardo, Ashley A. Olson, Leona H. Gagnon, Vivek M. Philip, William Valdar, Fernando Pardo-Manuel de Villena, James D. Jentsch, Ryan W. Logan, Colleen A. McClung, Donita L. Robinson, Elissa J. Chesler, Lisa M. Tarantino
PSYCHOPHARMACOLOGY
(2020)
Article
Behavioral Sciences
Shawn M. Aarde, Rylee M. Genner, Haley Hrncir, Arthur P. Arnold, James D. Jentsch
Summary: The study found that male mice with XY sex chromosome complement exhibited a higher overall error rate compared to female mice with XX sex chromosome complement during a reversal-learning task. XY mice showed more perseverative errors during the task, shorter prepotent-response latencies, and more frequent failures to sustain the observing response compared to XX mice. This suggests that sex-chromosome complement influences response selection in cognitive processes relevant to psychiatric/neurodevelopmental disorders and syndromes associated with sex-chromosome aneuploidies.
GENES BRAIN AND BEHAVIOR
(2021)
Article
Neurosciences
Amie L. Severino, Nitish Mittal, Joshua K. Hakimian, Nathanial Velarde, Ani Minasyan, Ralph Albert, Carlos Torres, Nicole Romaneschi, Camille Johnston, Suchi Tiwari, Alex S. Lee, Anna M. Taylor, Claire Gaveriaux-Ruff, Brigitte L. Kieffer, Christopher J. Evans, Catherine M. Cahill, Wendy M. Walwyn
Article
Neurosciences
Nitish Mittal, W. Todd Maddox, Timothy Schallert, Christine L. Duvauchelle
Article
Substance Abuse
Jared R. Bagley, Elissa J. Chesler, Vivek M. Philip, James D. Jentsch
Summary: Genetic factors play a role in voluntary ethanol consumption and pharmacokinetics, with different mouse populations showing varying levels of genetic diversity. The PWK/PhJ strain exhibits the highest ethanol consumption, and it was found that sex moderates genetic effects on voluntary ethanol drinking.
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
(2021)
Article
Neurosciences
Catherine B. Ashley, Ryan D. Snyder, James E. Shepherd, Catalina Cervantes, Nitish Mittal, Sheila Fleming, Jaxon Bailey, Maisie D. Nievera, Sharmin Islam Souleimanova, Bill Nyaoga, Lauren Lichtenfeld, Alicia R. Chen, W. Todd Maddox, Christine L. Duvauchelle
Summary: Ultrasonic vocalizations are known indicators of emotional processing and brain function. Acoustilytix, a web-based automated USV scoring tool, utilizes machine learning for high sensitivity and precision in call detection. Future improvements include machine-learning-based call type classification prediction.
Article
Neurosciences
Alyssa Moore, Jerome Linden, James D. Jentsch
Summary: The homozygous null for the Syn3 gene in mice showed a specific reversal effect on behavioral flexibility, resulting in an increased number of trials and an increase in perseverative behavior, while also reducing waiting impulsivity.
Article
Behavioral Sciences
Lauren S. Bailey, Jared R. Bagley, Rainy Dodd, Ashley Olson, Mikayla Bolduc, Vivek M. Philip, Laura G. Reinholdt, Stacey J. Sukoff Rizzo, Lisa Tarantino, Leona Gagnon, Elissa J. Chesler, James David Jentsch
Summary: This study examined reward sensitivity and impulsivity traits using different strains of mice, finding significant heritability for impulsive action, impulsive choice, waiting impulsivity, locomotor activity, and reward sensitivity. The research also identified these impulsive phenotypes as non-correlating, independent traits.
GENES BRAIN AND BEHAVIOR
(2021)
Article
Biochemistry & Molecular Biology
Jared R. Bagley, Arshad H. Khan, Desmond J. Smith, James D. Jentsch
Summary: Cocaine self-administration is a complex trait influenced by genetic variation. The use of laboratory animals and genetic association studies can provide insights into the neurogenetic influences on cocaine use. This study found that cocaine and saline self-administration were heritable traits, with a modest genetic correlation between the two. Genome-wide association studies identified significant genetic loci associated with cocaine self-administration. This research contributes to our understanding of the genetic and neurobiological factors underlying cocaine risk.
Article
Neurosciences
Lauren S. Bailey, Jared R. Bagley, James D. Wherry, Elissa J. Chesler, Anushree Karkhanis, James D. Jentsch, Lisa M. Tarantino
Summary: This study found that genetic background can influence the neuroadaptations induced by cocaine, which may contribute to understanding the biological mechanisms of cocaine addiction.
PSYCHOPHARMACOLOGY
(2023)
Meeting Abstract
Substance Abuse
S. M. Aarde, G. A. K. Golyakhovsky, J. D. Jentsch
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Lara A. Ray, Erica N. Grodin, Lorenzo Leggio, Anita J. Bechtholt, Howard Becker, Sarah W. Feldstein Ewing, James David Jentsch, Andrea C. King, Barbara J. Mason, Stephanie O'Malley, James MacKillop, Markus Heilig, George F. Koob
Summary: The scientific meeting at UCLA discussed the challenges and opportunities in translating neurobiological insights into advances in AUD treatment. Recommendations for the future include strengthening the clinical applicability of research findings to expedite knowledge translation into patient care.