Article
Pharmacology & Pharmacy
Francesco Petragnano, Irene Fasciani, Clotilde Mannoury la Cour, Benjamin di Cara, Gabriella Aloisi, Marco Carli, Shivakumar Kolachalam, Mario Rossi, Francesco Marampon, Marco Scarselli, Mark J. Millan, Roberto Maggio
Summary: This study investigates the affinity and activation of (+)-4-Propyl-9-hydroxynaphthoxazine on various monoamine receptors. It is found to have high affinity for hD(4.4), h5-HT1A, and h5-HT7 receptors, as well as hD(3) and hD(2L) receptors. It also strongly activates dopamine hD(3)-hD(2L) heterodimers. These findings are important for interpreting PET studies and may have implications for the treatment of Parkinson's disease and other disorders.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Clinical Neurology
D'bora Dreher Nabinger, Stefani Altenhofen, Alexis Buatois, Amanda Facciol, Julia Vasconcellos Peixoto, Julia Maria Kuhl da Silva, Diptendu Chatterjee, Gabriel Rubensam, Robert Gerlai, Carla Denise Bonan
Summary: This study investigated the effects of the dopamine D2/D3 receptor agonist quinpirole on the behavior, brain-derived neurotrophic factor (BDNF), and neurotransmitter levels in adult zebrafish. The results showed that quinpirole administration caused decreased locomotor activity, increased anxiety-like behaviors, memory impairment, and stereotypic swimming in zebrafish. Furthermore, quinpirole treatment also decreased the number of BDNF-immunoreactive cells and altered glutamate and serotonin levels in the zebrafish brain. These findings suggest that quinpirole administration in adult zebrafish can be a useful tool for studying the mechanisms underlying neurological disorders related to the dopaminergic system.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2023)
Article
Neurosciences
Mia I. Allen, Angela N. Duke, Susan H. Nader, Adrienne Adler-Neal, Kiran Solingapuram K. Sai, Beth A. Reboussin, H. Donald Gage, Ronald J. Voll, Akiva Mintz, Mark M. Goodman, Michael A. Nader
Summary: Brain imaging studies using PET have shown that long-term cocaine use is associated with lower levels of dopamine D2/D3 receptors and inconsistent effects on dopamine transporter availability. This study used PET imaging to examine the effects of cocaine self-administration on D2/D3 receptor availability and dopamine transporter availability in female monkeys. The results demonstrated sex differences in the relationship between D2/D3 receptor availability and vulnerability to long-term cocaine use, with baseline D2/D3 receptor availability only correlated with cocaine self-administration in the first week of exposure.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Cristina Cosi, Jean-Claude Martel, Agnes L. Auclair, Ginetta Collo, Laura Cavalleri, Peter Heusler, Ludovic Leriche, Florence Gaudoux, Pierre Sokoloff, Paul C. Moser, Silvia Gatti-McArthur
Summary: F17464 is a new potential antipsychotic with a unique profile, showing high affinity for dopamine receptor subtype 3 and serotonin receptor subtype 1a, while having lower affinity for dopamine receptor subtype 2. It has demonstrated various neurochemistry and behavioral effects, suggesting therapeutic potential for schizophrenia and autism.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Neurosciences
Paul W. Czoty, Aaron M. Tryhus, Kiran K. Solingapuram Sai, Susan H. Nader, Phillip M. Epperly
Summary: Identifying neurobiological characteristics that predict the development of cocaine use disorder would be valuable in prevention efforts. Brain dopamine receptors, specifically D2R and D3R, play important roles in mediating the abuse-related effects of cocaine. Analysis of data from studies on rhesus monkeys suggests that D2R availability in the caudate nucleus may be related to initial sensitivity to cocaine, while D3R sensitivity is associated with the dose at which monkeys acquired cocaine self-administration. These findings suggest the potential utility of D3R sensitivity as a biomarker for vulnerability and resilience to cocaine.
Article
Biochemistry & Molecular Biology
Ginna Uruena-Mendez, Andrea Dimiziani, Lidia Belles, Raphael Goutaudier, Nathalie Ginovart
Summary: Current research suggests that alterations in dopamine transmission in the striatum contribute to impulsivity and novelty-seeking, and may be related to a higher susceptibility to drug abuse. However, there is still debate about whether this susceptibility results from a hyperdopaminergic or hypodopaminergic state. In this study, rats with high impulsivity and novelty-seeking behaviors exhibited lower availability of D2/3 receptors and higher amphetamine-induced dopamine release in the striatum, which predicted higher levels of cocaine intake. Cocaine self-administration did not affect D2/3 receptor availability or impulsivity in these rats. Importantly, cocaine exposure led to a baseline-dependent decrease in stimulated dopamine release in high-impulsive/high novelty-seeking rats only, and to a baseline-dependent increase in novelty-seeking in low-impulsive/low novelty-seeking rats only. Overall, this study suggests that susceptibility to drug abuse is associated with an innate hyper-responsive dopamine system that promotes impulsive and novelty-seeking behaviors, and leads to stronger initial drug-reinforcing effects. However, with repeated cocaine use, tolerance to drug-induced dopamine elevations develops, resulting in compensatory increases in drug consumption to overcome reduced reward effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Milica Elek, Mariam Dubiel, Laura Mayer, Aleksandra Zivkovic, Thomas J. J. Mueller, Holger Stark
Summary: This article describes the use of BOPPY fluorophores for labeling dopamine D2 and D3 receptor ligands, obtaining compounds with fluorescent properties. This method is widely applicable.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Review
Biochemistry & Molecular Biology
Kyeong-Man Kim
Summary: Dopamine receptors, specifically D2R and D3R, play important roles in regulating mood, motivation, reward, and movement. While D2R are widely distributed across the brain, D3R are primarily found in specific areas related to cognitive and emotional functions. Despite their similarities, D2R and D3R have distinct regulatory properties involving desensitization, endocytosis, posttranslational modification, and interactions with other cellular components.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Bing Chen, Jiangang Xu, Simiao Chen, Tingting Mou, Ying Wang, Haojun Wang, Zhihan Zhang, Feifan Ren, Zheng Wang, Kangyu Jin, Jing Lu
Summary: This study found that dysregulation of the dopamine system contributes to depressive-like behaviors in rats, and the neurological functions regulated by hypocretin are severely affected in depression. It also found that suvorexant plays a role in alleviating depression by affecting the dopamine system.
JOURNAL OF AFFECTIVE DISORDERS
(2023)
Article
Biochemistry & Molecular Biology
Boeun Lee, Michelle Taylor, Suzy A. Griffin, Tamara McInnis, Nathalie Sumien, Robert H. Mach, Robert R. Luedtke
Summary: The study showed that N-phenylpiperazine analogs can selectively bind to the human D3 dopamine receptor with significant D3 vs. D2 binding selectivity, potentially leading to the development of pharmacotherapeutics for levodopa-induced dyskinesia in patients with Parkinson's disease.
Article
Chemistry, Medicinal
Gui-Long Tian, Chia-Ju Hsieh, Michelle Taylor, Aladdin A. Riad, Robert R. Luedtke, Robert H. Mach
Summary: The difference in the secondary binding site between D2R and D3R has been utilized to design compounds with selectivity for D3R. This study prepared a series of bitopic ligands based on Fallypride to improve the selectivity for D3R using various secondary binding fragments. The results showed that compounds with a small alkyl group containing a heteroatom exhibited improved D3R selectivity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Celine Legros, Anne Rojas, Clemence Dupre, Chantal Brasseur, Isabelle Riest-Fery, Olivier Muller, Jean-Claude Ortuno, Olivier Nosjean, Sophie-Penelope Guenin, Gilles Ferry, Jean A. Boutin
Summary: D3/D2 sub-specificity is a complex problem to solve due to the lack of easy structural biology of G-protein coupled receptors. This study used directed mutagenesis and basic binding experiments to explore a rational approach for the discovery of highly specific D3 ligands over D2 ligands. Stable expression of receptors in HEK cells was used to construct mutants and chimeras of D2 and D3 receptors, and their binding characteristics were analyzed using standard binding conditions. The study demonstrated the feasibility and potential of the approach.
Article
Biochemistry & Molecular Biology
Anna Kruyer, Jeffrey Parrilla-Carrero, Courtney Powell, Lasse Brandt, Stefan Gutwinski, Ariana Angelis, Reda M. Chalhoub, Thomas C. Jhou, Peter W. Kalivas, Davide Amato
Summary: Antipsychotic-induced dopamine supersensitivity is a problematic consequence of long-term antipsychotic treatment, characterized by motor abnormalities, refractory symptoms, and rebound psychosis. This phenomenon is associated with long-lasting synaptic plasticity and hyperexcitability in a subpopulation of D2 receptor-expressing neurons, leading to behavioral endophenotypes of treatment resistance and substance use disorder. Chemogenetic restoration of inhibitory postsynaptic currents may offer a novel therapeutic direction for preventing antipsychotic-induced supersensitivity.
MOLECULAR PSYCHIATRY
(2021)
Article
Chemistry, Medicinal
Francisco O. Battiti, Saheem A. Zaidi, Vsevolod Katritch, Amy Hauck Newman, Alessandro Bonifazi
Summary: This study investigates the role of regio- and stereochemistry in cyclic aliphatic linkers tethering pharmacophores targeting dopamine D-2 and D-3 receptors, introducing potent and selective agonists while modulating subtype selectivity in a stereospecific manner. The findings demonstrate a novel approach to modulate dopaminergic ligand pharmacology and introduce a new class of optically active cyclic linkers that can be utilized in expanding bitopic drug design towards other GPCRs. Extensive molecular docking studies support the pharmacological observations presented in the study.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
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)
Review
Cell Biology
Robert L. Haining, Cindy Achat-Mendes
NEURAL REGENERATION RESEARCH
(2017)
Article
Neurosciences
Brid A. Nic Dhonnchadha, Jonathan J. Szalay, Cindy Achat-Mendes, Donna M. Platt, Michael W. Otto, Roger D. Spealman, Kathleen M. Kantak
NEUROPSYCHOPHARMACOLOGY
(2010)
Article
Neurosciences
Cindy Achat-Mendes, Brid A. Nic Dhonnchadha, Donna M. Platt, Kathleen M. Kantak, Roger D. Spealman
NEUROPSYCHOPHARMACOLOGY
(2012)
Article
Behavioral Sciences
Cindy Achat-Mendes, Laurie J. Lynch, Katherine A. Sullivan, Eric J. Vallender, Gregory M. Miller
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2012)
Article
Neurosciences
Cindy Achat-Mendes, Glenn R. Valdez, Donna M. Platt, James K. Rowlett, Roger D. Spealman
PSYCHOPHARMACOLOGY
(2009)
Article
Neurosciences
Cindy Achat-Mendes, Donna M. Platt, Amy H. Newman, Roger D. Spealman
PSYCHOPHARMACOLOGY
(2009)
Article
Biochemistry & Molecular Biology
Jackson Fink, Heather Pathak, John Smith, Cindy Achat-Mendes, Robert L. Haining
Article
Communication
Kelsey M. Gray, Cindy Achat-Mendes, Ann Cale Kruger, Tashi Lhamo, Rinchen Wangyal, Gelek Gyatso, Carol M. Worthman
Summary: Led by the Dalai Lama, this study examines the motivations and engagement behaviors of Tibetan Buddhist monastic students in science education. The findings suggest that these students are motivated by the belief that studying science positively impacts their Buddhist studies, and they encourage fellow scholars to engage with science concepts.
FRONTIERS IN COMMUNICATION
(2022)
Article
Communication
Carol M. Worthman, Ann Cale Kruger, Cindy Achat-Mendes, Tashi Lhamo, Rinchen Wangyal, Gelek Gyatso, Kelsey M. Gray
Summary: In a globalized world where division and disinformation pose major challenges, the initiative to incorporate western science in Tibetan Buddhist education curriculum serves as a significant case study in successful cultural outreach and exchange. By examining initial cultural conditions and learning mechanisms facilitating boundary crossing, the study demonstrates how Tibetan Buddhist monastic students engage with science on their own terms, highlighting the benefits of cross-community communication.
FRONTIERS IN COMMUNICATION
(2021)
Article
Education, Scientific Disciplines
Jennifer Hurst-Kennedy, Michael Saum, Cindy Achat-Mendes, Allison D'Costa, Elisabeth Javazon, Shoshana Katzman, Ernest Ricks, Alessandra Barrera
JOURNAL OF MICROBIOLOGY & BIOLOGY EDUCATION
(2020)
Article
Pharmacology & Pharmacy
Cindy Achat-Mendes, Donna M. Platt, Roger D. Spealman
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2012)
Article
Neurosciences
Cindy Achat-Mendes, Karen L. Anderson, Yossef Itzhak
NEUROPSYCHOPHARMACOLOGY
(2007)
Article
Neurosciences
C Achat-Mendes, SF Ali, Y Itzhak
NEUROPSYCHOPHARMACOLOGY
(2005)
Review
Biochemistry & Molecular Biology
Y Itzhak, C Achat-Mendes