Article
Neurosciences
Carla Carratala-Ros, Regulo Olivares-Garcia, Andrea Martinez-Verdu, Edgar Arias-Sandoval, John D. Salamone, Merce Correa
Summary: The study found that the antidepressant bupropion can improve active behaviors in depressed patients and reversed the low-effort bias induced by the dopaminergic drug tetrabenazine in rodents.
PSYCHOPHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Xin-Yue Wang, Wen-Bin Jia, Xiang Xu, Rui Chen, Liang-Biao Wang, Xiao-Jing Su, Peng-Fei Xu, Xiao-Qing Liu, Jie Wen, Xiao-Yuan Song, Yuan-Yuan Liu, Zhi Zhang, Xin-Feng Liu, Yan Zhang
Summary: This study reveals a pathway involving vesicular glutamate transporter 3 neurons and dopamine neurons that plays a crucial role in chronic pain and comorbid anhedonia-like behavior. Chronic neuropathic pain dampens the transmission of glutamate and the neural excitability in this pathway. Activation of this pathway can alleviate pain and comorbid anhedonia-like behavior, while inhibition of this pathway leads to pain-like reflexive hypersensitivity and anhedonia-like behavior.
NATURE COMMUNICATIONS
(2023)
Article
Behavioral Sciences
Rose E. Presby, Renee A. Rotolo, Erin M. Hurley, Sarah M. Ferrigno, Cayla E. Murphy, Haley P. McMullen, Pranally A. Desai, Emma M. Zorda, Felicita B. Kuperwasser, Carla Carratala-Ros, Merce Correa, John D. Salamone
Summary: Selective serotonin transport (SERT) inhibitors like fluoxetine are commonly prescribed for depression, but they may exacerbate motivational deficits in some people. In animal models, fluoxetine suppressed high effort activities in both male and female rats, with significant differences in behavior between sexes observed. The suppressive effects of fluoxetine on voluntary physical activity may have implications for understanding psychiatric disorders.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2021)
Article
Neurosciences
John D. Salamone, Alev Ecevitoglu, Carla Carratala-Ros, Rose E. Presby, Gayle A. Edelstein, Reileigh Fleeher, Renee A. Rotolo, Nicolette Meka, Sonya Srinath, Jamie C. Masthay, Merce Correa
Summary: Instrumental behavior is a complex process influenced by factors such as conditioning, motivation, affect, and decision-making. Assessing the temporal characteristics and biophysical measures of instrumental behavior can provide insights into its mechanisms. Dopamine antagonism and depletion can lead to specific deficits in operant behavior, and further research is needed to understand the complexities of dopamine's role. This research can also shed light on dysfunctions seen in conditions such as depression and Parkinson's disease.
BRAIN RESEARCH BULLETIN
(2022)
Article
Multidisciplinary Sciences
Tasuku Kayama, Yuji Ikegaya, Takuya Sasaki
Summary: Dopaminergic neurons in the VTA play a crucial role in reward processing and peripheral immunity. Optogenetic phasic stimulation of these neurons increases serum cytokine levels, while encounters with females also lead to elevated serum IL-2 levels. These findings have important implications for the treatment and management of immune-related disorders.
SCIENTIFIC REPORTS
(2022)
Article
Neurosciences
Tamara Markovic, Christian E. Pedersen, Nicolas Massaly, Yvan M. Vachez, Brian Ruyle, Caitlin A. Murphy, Kavitha Abiraman, Jung Hoon Shin, Jeniffer J. Garcia, Hye Jean Yoon, Veronica A. Alvarez, Michael R. Bruchas, Meaghan C. Creed, Jose A. Moron
Summary: Anhedonia-like states in inflammatory pain are mediated through decreased activity of mesolimbic dopamine neurons, which are triggered by increased inhibitory control from the rostromedial tegmental nucleus onto ventral tegmental area dopamine neurons. Selective activation of ventral tegmental area dopamine neurons can restore motivation and hedonic responses.
NATURE NEUROSCIENCE
(2021)
Article
Behavioral Sciences
Andrew Dieterich, Joseph Floeder, Karina Stech, Jay Lee, Prachi Srivastava, David J. Barker, Benjamin A. Samuels
Summary: The study revealed that BLA-NAc neurons play a nuanced role in mediating reward behaviors, with activation of these neurons attenuating maladaptive behaviors induced by chronic stress, including avoidance and reward-seeking behaviors, without affecting free-feeding.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Daniel J. Christoffel, Jessica J. Walsh, Paul Hoerbelt, Boris D. Heifets, Pierre Llorach, Ricardo C. Lopez, Charu Ramakrishnan, Karl Deisseroth, Robert C. Malenka
Summary: The study reveals that dopamine and serotonin modulate excitatory synaptic transmission in the nucleus accumbens in input-specific ways, influencing motivated behaviors differently. Endogenous release of DA and 5-HT, as well as optogenetic inhibition, alter the behavioral effects of drugs in distinct manners.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Dan P. Covey, Edith Hernandez, Miguel A. Lujan, Joseph F. Cheer
Summary: The study found that dopamine release in the nucleus accumbens responds differently to cues signaling increasing cost of reward. Endocannabinoid signaling facilitates goal-seeking and nucleus accumbens dopamine release, while chronic MAGL treatment stably facilitates goal-seeking and dopamine encoding without the development of tolerance.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Sai Sun, Chuhua Cai, Rongjun Yu
Summary: When individuals make value-based decisions, expected rewards play a major role in determining response times. Risk, on the other hand, affects attention deployment and is dependent on the magnitude of potential rewards and the level of risk. The processing of mean rewards activates the striatum, which is connected to the amygdala and superior frontal gyrus, while risk processing activates the anterior insula, which is connected to the ventromedial prefrontal cortex and anterior midcingulate cortex. These findings provide insights into how attention, motivation, and brain networks are modulated by reward and risk in non-decision contexts.
Article
Behavioral Sciences
Judith Gruber, Ruth Hanssen, Mishal Qubad, Aicha Bouzouina, Vivi Schack, Hannah Sochor, Carmen Schiweck, Mareike Aichholzer, Silke Matura, David A. Slattery, Yurdaguel Zopf, Stephanie L. Borgland, Andreas Reif, Sharmili Edwin Thanarajah
Summary: Type 2 diabetes and major depressive disorder (MDD) are highly comorbid and leading causes of disability. This review discusses the potential molecular mechanisms underlying their association by examining the effects of insulin on dopaminergic signaling and behavior in the brain. It also explores the impact of insulin resistance on depressive symptoms and anhedonia, and its relevance for treatment strategies.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Review
Behavioral Sciences
Bowen J. Fung, Elissa Sutlief, Marshall G. Hussain Shuler
Summary: Time perception and reward processing interact through a common dopaminergic mechanism, as supported by both neurobiological and behavioral studies.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Article
Neurosciences
Emily L. Errante, Marilyn Chakkalamuri, Oreoluwa Akinbo, Samantha E. Yohn, John D. Salamone, Leslie Matuszewich
Summary: Sex differences were found in training variables, with males exhibiting higher lever presses, ratios, and active lever times. HAL administration reduced behavior in both sexes for high-valued reward and increased chow consumption in food restricted males. Despite differences in training, HAL decreased behavior similarly in both sexes, suggesting a common D2 mechanism.
PSYCHOPHARMACOLOGY
(2021)
Article
Behavioral Sciences
Carla Carratala-Ros, Laura Lopez-Cruz, Andrea Martinez-Verdu, Regulo Olivares-Garcia, John D. Salamone, Merce Correa
Summary: Fluoxetine can improve behavioral activation in depressed patients, but it cannot reverse the anergic effects of dopamine depletion. The study found that fluoxetine was ineffective in treating anergia induced by dopamine depletion.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2021)
Article
Neurosciences
Kurt M. Fraser, Heather J. Pribut, Patricia H. Janak, Ronald Keiflin
Summary: Reward seeking requires coordination of motor programs. Midbrain dopamine neurons are critical for reinforcement and learning. Ventral tegmental area (VTA) dopamine neurons imbue actions and cues with motivational value, allowing flexible pursuit, whereas substantia nigra (SNc) dopamine neurons support precise, action-specific learning. This heterogeneous dopamine system supports unique forms of instrumental learning and reward-seeking strategies.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Psychology, Biological
Rose E. Presby, Renee A. Rotolo, Sydney Katz, Zoha Sarwat, Merce Correa, John D. Salamone
Summary: Inflammation is associated with motivational deficits in depression and other disorders. Experiments using lipopolysaccharide (LPS) have shown that inflammation can impair motivated behavior in humans and rodents. In addition to exerting effects on instrumental behavior, LPS also directly affects primary food motivation.
PHYSIOLOGY & BEHAVIOR
(2023)
Article
Pharmacology & Pharmacy
Jan H. Voss, Haneen Al-Hroub, Robin Gedschold, Jennifer M. Dietrich, Evelyn Gaffal, Marieta Toma, Stefan Kehraus, Gabriele M. Koenig, Peter Brust, Bernd K. Fleischmann, Daniela Wenzel, Winnie Deuther-Conrad, Christa E. Mueller
Summary: G protein is identified as a potential drug target for treating complex diseases. The development of specific radiotracers allows for disease diagnosis and research.
Article
Biochemistry & Molecular Biology
Mariam Tahoun, Marianne Engeser, Luca Svolacchia, Paul Martin Sander, Christa E. E. Mueller
Summary: This study investigates the stability and degradation of the oxygen-complexing prosthetic group of hemoglobin, heme, under various conditions expected to occur during fossilization. The results reveal that heme is most stable under anaerobic reductive conditions and least stable in the presence of H2O2. The presence of oxygen and H2O2 leads to the cleavage of heme and the formation of hematinic acid. The role of iron cation in heme degradation is confirmed, as heme lacking iron remains more stable. This study provides valuable insights into the fate of heme during fossilization.
Editorial Material
Chemistry, Medicinal
Jeffrey Aube, Craig W. Lindsley, Christa E. Mueller
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Multidisciplinary Sciences
Jan H. Voss, Max Cruesemann, Christian R. O. Bartling, Stefan Kehraus, Asuka Inoue, Gabriele M. Koenig, Kristian Stromgaard, Christa E. Mueller
Summary: This study investigated the inhibitory effects of macrocyclic depsipeptides YM-254890 and FR900359 on Gaq/11 proteins and observed significant differences in dissociation kinetics between these compounds and their hydrogenated, tritium-labeled derivatives. Results showed that small structural modifications had a major impact on the residence time of the macrocyclic depsipeptides. FR exhibited pseudo-irreversible binding, while YM had a faster dissociation rate. The isopropyl anchor in FR and some derivatives was found to be essential for slow dissociation. These findings provide a basis for future drug design strategies to modulate residence times of macrocyclic Gq protein inhibitors, which play a crucial role in therapeutic outcomes.
Article
Chemistry, Multidisciplinary
Tobias Claff, Jonathan G. Schlegel, Jan H. Voss, Victoria J. Vaassen, Renato H. Weisse, Robert K. Y. Cheng, Sandra Markovic-Mueller, Denis Bucher, Norbert Straeter, Christa E. Mueller
Summary: The authors report the crystal structures of A(2A)AR in complex with Etrumadenant, revealing a previously unknown interaction. These findings have implications for the design of selective receptor antagonists.
COMMUNICATIONS CHEMISTRY
(2023)
Editorial Material
Chemistry, Medicinal
Jeffrey Aube, Craig W. Lindsley, Christa E. Mueller
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Fatma Al-Rubaiai, Zakiya Zahran Al-Shariqi, Khalsa S. Al-Shabibi, John Husband, Asmaa M. Al-Hattali, Marcia Goettert, Stefan Laufer, Younis Baqi, Syed Imran Hassan, Majekodunmi O. Fatope
Summary: Maytenus dhofarensis Sebsebe is a shrub native to Oman that causes shivering attacks on grazed goats. Chemical investigation of its fruits and stems led to the discovery of new compounds, including a sesquiterpene pyridine alkaloid and lignanolactone. The structures and relative configurations of these compounds were determined through various analytical techniques. One of the compounds showed no inhibition activity on a kinase enzyme, while another compound exhibited strong antioxidant activity.
Article
Neurosciences
Carla Carratala-Ros, Andrea Martinez-Verdu, Regulo Olivares-Garcia, John D. Salamone, Merce Correa
Summary: This study investigates the sex differences in rodent models of depression and the treatment response to antidepressants with different mechanisms of action. The findings suggest that dopaminergic antidepressants are more effective in improving anergia in both male and female rodents compared to serotonin reuptake inhibitors. This study highlights the importance of considering sex differences in depression research.
PSYCHOPHARMACOLOGY
(2023)
Article
Neurosciences
Paula Matas-Navarro, Carla Carratala-Ros, Regulo Olivares-Garcia, Andrea Martinez-Verdu, John D. Salamone, Merce Correa
Summary: This study compared the motivation performance in effort-based decision-making tasks between male and female mice. The results showed that female mice were more willing to exert effort for reinforcers than males. The age factor also had an impact on motivation performance. Therefore, it is important to take into account differences in sex and age when evaluating willingness to exert effort for specific reinforcers.
PSYCHOPHARMACOLOGY
(2023)
Article
Neurosciences
Alev Ecevitoglu, Gayle A. Edelstein, Rose E. Presby, Renee A. Rotolo, Jen-Hau Yang, Taina Quiles, Kevin Okifo, Ryan T. Conrad, Ashley Kovach, Merce Correa, John D. Salamone
Summary: Cariprazine shows a tendency to decrease effort-related behavior in rats and mice, indicating its potential for treating negative symptoms. It acts as a D2-family antagonist, suggesting a different pharmacological regulation for avolition compared to other negative symptoms.
PSYCHOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Michal Zaluski, Tadeusz Karcz, Anna Drabczynska, Christin Vielmuth, Agnieszka Olejarz-Maciej, Monika Gluch-Lutwin, Barbara Mordyl, Agata Siwek, Grzegorz Satala, Christa E. Muller, Katarzyna Kiec-Kononowicz
Summary: Multitarget drugs designed with a hybrid dopamine-xanthine core have potential as drug candidates for neurodegenerative diseases. Further development of monoamine oxidase B (MAO-B) inhibitors with A(2A) adenosine receptor (A(2A)AR) antagonistic properties led to additional phosphodiesterase-4 and -10 (PDE4/10) inhibition and/or dopamine D-2 receptor (D2R) agonistic activity. The compounds showed MAO-B inhibition combined with A(2A)AR affinity, and some compounds exhibited enhanced PDE-inhibitory and D2R-agonistic activity through structural modifications. The multitarget drugs also demonstrated antioxidant properties in vitro and neuroprotective effects in a cellular model.
Article
Biochemistry & Molecular Biology
Nina Geiger, Viktoria Diesendorf, Valeria Roll, Eva-Maria Koenig, Helena Obernolte, Katherina Sewald, Julian Breidenbach, Thanigaimalai Pillaiyar, Michael Guetschow, Christa E. Mueller, Jochen Bodem
Summary: Recently, we investigated novel pyridyl indole esters and peptidomimetics as potent inhibitors of SARS-CoV-2 main protease. We analyzed the impact of these compounds on viral replication and found that their effectiveness varied in different cell lines. In Huh-7 cells, the protease inhibitors suppressed viral replication by up to 5 orders of magnitude, while in Calu-3 cells, suppression by 2 orders of magnitude was achieved. Three pyridin-3-yl indole-carboxylates showed antiviral activity in all cell lines and also in human precision-cut lung slices.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Daniel Marx, Mohamed Wessam Alnouri, Sophie Clemens, Robin Gedschold, Yvonne Riedel, Ghazl Al Hamwi, Thanigaimalai Pillaiyar, Jorg Hockemeyer, Vigneshwaran Namasivayam, Christa E. Mueller
Summary: This study discovered a xanthine derivative that activates the main variant of MRGPRX4, and optimization resulted in analogs with high potency and metabolic stability. These compounds are promising tool compounds for exploring the potential of MRGPRX4 as a future drug target.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)