Article
Medicine, Research & Experimental
Yongsheng Zhu, Kejia Wang, Tengfei Ma, Yuanyuan Ji, Yin Lou, Xiaoyu Fu, Ye Lu, Yige Liu, Wei Dang, Qian Zhang, Fangyuan Yin, Kena Wang, Bing Yu, Hongbo Zhang, Jianghua Lai, Yunpen Wang
Summary: This study identified neural pathways involved in controlling depressive-like behaviors and acute withdrawal symptoms after morphine withdrawal. Furthermore, a new DBS treatment protocol was developed to reverse abnormal plasticity and alleviate withdrawal symptoms and depressive-like behaviors.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Neurosciences
Kyle A. Windisch, Michelle Morochnik, Brian Reed, Mary Jeanne Kreek
Summary: The mu opioid receptor antagonist/kappa opioid receptor (KOR) partial agonist nalmefene (NMF) did not significantly reduce cocaine intake, but acute pretreatment of 1 mg/kg NMF significantly potentiated cocaine motivation. Further research with KOR selective partial or full agonists is required to determine their effect on cocaine reinforcement.
Article
Biochemistry & Molecular Biology
Nicholas S. Akins, Mohammed F. Salahuddin, Pankaj Pandey, Seong Jong Kim, Fakhri Mahdi, Md Imdadul H. Khan, Emaya M. Moss, Charlie J. Worth, Madeline M. Keane, Amar G. Chittiboyina, Robert J. Doerksen, Jason J. Paris, Hoang V. Le
Summary: The KOR is involved in the regulation of reward and mood, and drug abuse increases its activation. Long-acting KOR antagonists have been shown to alleviate withdrawal symptoms, but their use in humans comes with safety concerns. This study found that a short-acting KOR antagonist showed efficacy in reducing withdrawal behavior in mice, and computational studies provided insights for the design of future antagonists.
ACS CHEMICAL NEUROSCIENCE
(2023)
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
Clinical Neurology
Andrea Cippitelli, Gilles Zribi, Lawrence Toll
Summary: PPL-103 has shown potential as a pharmacotherapy for the treatment of cocaine use disorder (CUD). It reduces self-administration of cocaine, decreases motivation for cocaine, and attenuates binge-like cocaine taking. PPL-103 also reduces priming- and cue-induced reinstatement of cocaine seeking. Tolerance development was not observed with repeated PPL-103 treatment.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2022)
Article
Medicine, Research & Experimental
Henry K. Karlsson, Lauri Tuominen, Semi Helin, Paulina Salminen, Pirjo Nuutila, Lauri Nummenmaa
Summary: Bariatric surgery is the most effective method for treating morbid obesity, with significant individual variability in postoperative weight outcomes. Brain receptor systems such as MOR may play a key role in predicting weight development post-surgery, offering new potential for treatment possibilities.
Article
Pharmacology & Pharmacy
Dasiel O. Borroto-Escuela, Karolina Wydra, Ramon Fores-Pons, Lakshmi Vasudevan, Wilber Romero-Fernandez, Malgorzata Frankowska, Luca Ferraro, Sarah Beggiato, Minerva Crespo-Ramirez, Alicia Rivera, Luisa L. Rocha, Miguel Perez de la Mora, Christophe Stove, Malgorzata Filip, Kjell Fuxe
Summary: The widespread distribution of heteroreceptor complexes with allosteric receptor-receptor interactions in the CNS plays a key role in learning, memory, and the development of substance use disorders like morphine and cocaine use disorders. These complexes could be potential pharmacological targets to modulate reward and substance use disorders.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Siavash Shahbazi Nia, Mohammad Anwar Hossain, Guangchen Ji, Sravan K. Jonnalagadda, Samuel Obeng, Md Ashrafur Rahman, Ali Ehsan Sifat, Saeideh Nozohouri, Collin Blackwell, Dhavalkumar Patel, Jon Thompson, Scott Runyon, Takato Hiranita, Christopher R. McCurdy, Lance McMahon, Thomas J. Abbruscato, Paul C. Trippier, Volker Neugebauer, Nadezhda A. German
Summary: Based on the structure of gliotoxin, two chemotypes with selective affinity to the kappa opioid receptor (KOR) were synthesized. Through medicinal chemistry and structure-activity relationship (SAR) studies, the required structural features for high affinity were identified, and advanced molecules with favorable properties were prepared. Compound 2 was shown to block the pain-relieving effect of a KOR agonist both in vitro and in vivo, indicating its potential application as a pain therapeutic.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Brian Reed, Michael Miller, Mayako Michino, Eduardo R. Butelman, Ariel Ben-Ezra, Philip Pikus, Michelle Morochnik, Yuli Kim, Amy Ripka, Joseph Vacca, Mary Jeanne Kreek
Summary: In this study, a novel kappa receptor agonist scaffold was developed and the modulation of receptor activity and complex function was demonstrated by altering the functional groups in the compounds. This research is important for understanding the intricacies of receptor signaling and developing biased drugs.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Neurosciences
J. D. Lorente, J. Cuitavi, L. Rullo, S. Candeletti, P. Romualdi, L. Hipolito
Summary: This study analyzed the effects of pain on negative affect in different sexes and time courses, as well as the involvement of the dynorphinergic and corticotropin releasing factor systems in these pain-related behaviors. The results showed sex and time-dependent anxiety- and anhedonia-like behaviors induced by pain in female rats. The recruitment of KOR/DYN in the NAc was identified as a key neurological substrate mediating pain-induced behavioral alterations.
Article
Behavioral Sciences
Luke A. Jelen, James M. Stone, Allan H. Young, Mitul A. Mehta
Summary: This article reviews the dysregulation of the opioid system in depression and the potential of pharmacological modulators of mu, delta, and kappa opioid receptors for the treatment of depression. The review presents evidence from animal and clinical studies supporting the dysregulation of the opioid system in depression, the modulation of behavioral processes and brain regions associated with depression by opioids, and the modulation of antidepressant responses by opioids. The review also evaluates clinical trials examining the safety and efficacy of opioidergic agents in depression and explores the involvement of the opioid system in the effects of other treatments, such as ketamine, that exert antidepressant effects through non-opioid actions. Furthermore, the review explores the neurochemical and molecular mechanisms underlying the therapeutic effects of opioid system engagement, providing a rationale for further investigation into this relevant target in depression treatment.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2022)
Article
Multidisciplinary Sciences
Julong Wei, Tova Y. Lambert, Aditi Valada, Nikhil Patel, Kellie Walker, Jayna Lenders, Carl J. Schmidt, Marina Iskhakova, Adnan Alazizi, Henriette Mair-Meijers, Deborah C. Mash, Francesca Luca, Roger Pique-Regi, Michael J. Bannon, Schahram Akbarian
Summary: This study found that chronic exposure to opioids results in broad transcriptional changes in glial cells, including upregulation of genes associated with immune response and downregulation of synaptic signaling and plasticity genes. It also identified certain genes that are linked to risk of substance use in the population.
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Kevin Clare, Chelsea Pan, Gloria Kim, Kicheon Park, Juan Zhao, Nora D. Volkow, Zhicheng Lin, Congwu Du
Summary: The study revealed increased density of D2r-positive cells in the medial prefrontal cortex and ventral tegmental area of both male and female mice passively exposed to chronic cocaine, alongside an overall decrease in neuronal density. Higher levels of Drd2 mRNA in the mPFC and Dstr of female mice exposed to cocaine suggest limited sensitivity of the method used. This shift in neuronal phenotype and potential cognitive impairments warrant further investigation.
FRONTIERS IN PHARMACOLOGY
(2021)
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
Neurosciences
Rachel J. Donahue, Archana Venkataraman, F. Ivy Carroll, Edward G. Meloni, William A. Carlezon
BIOLOGICAL PSYCHIATRY
(2016)
Editorial Material
Neurosciences
John H. Krystal, Anissa Abi-Dargham, Schahram Akbarian, Amy F. T. Arnsten, Deanna M. Barch, Carrie E. Bearden, David L. Braff, E. Sherwood Brown, Edward T. Bullmore, William A. Carlezon, Cameron S. Carter, Edwin H. Cook, Zafiris Jeff Daskalakis, Ralph J. DiLeone, Ronald S. Duman, Anthony A. Grace, Ahmad R. Hariri, Paul J. Harrison, Noboru Hiroi, Paul J. Kenny, Joel E. Kleinman, Andrew D. Krystal, David A. Lewis, Barbara K. Lipska, Stephen R. Marder, Graeme F. Mason, Daniel H. Mathalon, Colleen A. McClung, Christopher J. McDougle, Andrew M. McIntosh, Francis J. McMahon, Karoly Mirnics, Lisa M. Monteggia, Rajesh Narendran, Eric J. Nestler, Alexander Neumeister, Michael C. O'Donovan, Dost Ongur, Carmine M. Pariante, Martin P. Paulus, Godfrey Pearlson, Mary L. Phillips, Daniel S. Pine, Diego A. Pizzagalli, Mikhail V. Pletnikov, J. Daniel Ragland, Judith L. Rapoport, Kerry J. Ressler, Scott J. Russo, Gerard Sanacora, Akira Sawa, Alan F. Schatzberg, Yavin Shaham, Simone G. Shamay-Tsoory, Pamela Sklar, Matthew W. State, Murray B. Stein, Stephen M. Strakowski, Stephan F. Taylor, Gustavo Turecki, Bruce I. Turetsky, Myrna M. Weissman, Venetia Zachariou, Carlos A. Zarate, Jon-Kar Zubieta
BIOLOGICAL PSYCHIATRY
(2016)
Article
Psychology, Clinical
William A. Carlezon, Andrew D. Krystal
DEPRESSION AND ANXIETY
(2016)
Article
Neurosciences
Stephanie K. Nygard, Nicholas J. Hourguettes, Gabe G. Sobczak, William A. Carlezon, Michael R. Bruchas
JOURNAL OF NEUROSCIENCE
(2016)
Editorial Material
Clinical Neurology
Heather I. Rieff, Jonelle K. Drugan, Thomas R. Cheever, Ashlee Van't Veer, Glen H. Nuckolls, Stephen I. Katz
Review
Clinical Neurology
Franziska Hopfner, Dietrich Haubenberger, Wendy R. Galpern, Katrina Gwinn, Ashlee Van't Veer, Samantha White, Kailash Bhatia, Charles H. Adler, David Eidelberg, William Ondo, Glenn T. Stebbins, Caroline M. Tanner, Rick C. Helmich, Fred A. Lenz, Roy V. Sillitoe, David Vaillancourt, Jerrold L. Vitek, Elan D. Louis, Holly A. Shill, Matthew P. Frosch, Tatiana Foroud, Gregor Kuhlenbaeumer, Andrew Singleton, Claudia M. Testa, Mark Hallett, Rodger Elble, Guenther Deuschl
PARKINSONISM & RELATED DISORDERS
(2016)
Article
Endocrinology & Metabolism
Edward G. Meloni, Archana Venkataraman, Rachel J. Donahue, William A. Carlezon
PSYCHONEUROENDOCRINOLOGY
(2016)
Article
Behavioral Sciences
Ashlee Van't Veer, Karen L. Smith, Bruce M. Cohen, William A. Carlezon, Anita J. Bechtholt
BRAIN AND BEHAVIOR
(2016)
Article
Neurosciences
Audrey M. Wells, Elysia Ridener, Clinton A. Bourbonais, Woori Kim, Harry Pantazopoulos, F. Ivy Carroll, Kwang-Soo Kim, Bruce M. Cohen, William A. Carlezon
JOURNAL OF NEUROSCIENCE
(2017)
Article
Neurosciences
Hugo A. Tejeda, Jocelyn Wu, Alana R. Kornspun, Marco Pignatelli, Vadim Kashtelyan, Michael J. Krashes, Brad B. Lowell, William A. Carlezon, Antonello Bonci
Article
Neurosciences
Galen Missig, Emery L. Mokler, James O. Robbins, Abigail J. Alexander, Christopher J. McDougle, William A. Carlezon
NEUROPSYCHOPHARMACOLOGY
(2018)
Article
Endocrinology & Metabolism
Alexis E. Whitton, Ashlee Van't Veer, Pragya Kakani, Daniel G. Dillon, Manon L. Ironside, Anja Haile, David J. Crowley, Diego A. Pizzagalli
PSYCHONEUROENDOCRINOLOGY
(2017)
Article
Neurosciences
Andre Der-Avakian, Manoranjan S. D'Souza, David N. Potter, Elena H. Chartoff, William A. Carlezon, Diego A. Pizzagalli, Athina Markou
PSYCHOPHARMACOLOGY
(2017)
Article
Neurosciences
Kenneth M. McCullough, Filomene G. Morrison, Jakob Hartmann, William A. Carlezon, Kerry J. Ressler
Meeting Abstract
Neurosciences
Diego Pizzagalli, Alexis Whitton, Ashlee Van't Veer, Rachel Donahue, William Carlezon
BIOLOGICAL PSYCHIATRY
(2017)