Article
Medicine, Research & Experimental
Laia Alegre-Zurano, Paula Berbegal-Saez, Miguel A. Lujan, Lidia Cantacorps, Ana Martin-Sanchez, Alba Garcia-Baos, Olga Valverde
Summary: Cocaine is a widely consumed drug that affects brain areas responsible for reinforcement and motivation. This study found that cannabidiol has protective effects against cocaine addiction and reduces cocaine intake and craving. However, it has minimal effects on cocaine withdrawal and cravings.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Veronica Lunerti, Hongwu Li, Federica Benvenuti, Qianwei Shen, Ana Domi, Laura Soverchia, Rita Maria Concetta Di Martino, Giovanni Bottegoni, Carolina L. Haass-Koffler, Nazzareno Cannella
Summary: Tobacco use disorder is a worldwide health problem with limited efficacy in available medications. A study found that ARN15381, a multitarget compound with FAAH inhibition and DRD3 partial agonist activity, reduced nicotine self-administration in rats, suggesting the potential clinical importance of a multitarget approach in the treatment of tobacco use disorder.
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
Biology
Xiaojie Liu, Casey R. Vickstrom, Hao Yu, Shuai Liu, Shana Terai Snarrenberg, Vladislav Friedman, Lianwei Mu, Bixuan Chen, Thomas J. Kelly, David A. Baker, Qing-song Liu
Summary: This study demonstrates that Epac2 in the mesolimbic dopamine system promotes cocaine reinforcement by enhancing dopamine release. Conditional knockout or inhibition of Epac2 reduces cocaine self-administration in mice, while Epac2 agonism increases dopamine release. This mechanism plays a crucial role in the reinforcing effects of cocaine.
Article
Substance Abuse
Matthew J. Horchar, Joy L. Kappesser, Maria R. Broderick, Makayla R. Wright, Justin R. Yates
Summary: This study found that the GluN2B-selective antagonist Ro 63-1908 and the NMDA receptor channel blocker MK-801 can increase the overall demand for cocaine and reduce demand elasticity, but do not affect demand intensity.
DRUG AND ALCOHOL DEPENDENCE
(2022)
Article
Neurosciences
Timothy J. Collier, Lauren Begg, Jennifer A. Stancati, Natosha M. Mercado, Rhyomi C. Sellnow, Ivette M. Sandoval, Caryl E. Sortwell, Kathy Steece-Collier
Summary: Dopamine depletion in Parkinson's disease can cause maladaptive changes in striatal medium spiny neurons, leading to the emergence of levodopa-induced dyskinesia (LID). Blocking CaV1.3 calcium channels in the striatum can prevent spine loss and reduce LID. In this study, the combination of the CaV1 L-type channel antagonist isradipine and the D2/D3 dopamine receptor agonist quinpirole was investigated. Surprisingly, quinpirole monotherapy was more effective in reducing dyskinesia severity and preventing abnormal mushroom spine formation, while the co-administration of isradipine weakened its efficacy.
EXPERIMENTAL NEUROLOGY
(2023)
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
Pharmacology & Pharmacy
Michelle R. Doyle, Agnieszka Sulima, Kenner C. Rice, Gregory T. Collins
Summary: The study found that histories of responses maintained by drugs from different pharmacological classes have differential impacts on the development of the high-responder phenotype when MDPV is available for self-administration. Response-contingent cocaine and noncontingent cocaine can prevent the MDPV high-responder phenotype, while histories of responding maintained by fentanyl, nicotine, or ketamine may facilitate its development.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2021)
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
Neurosciences
Shayna L. O'Connor, Gary Aston-Jones, Morgan H. James
Summary: Heightened sensation seeking is associated with an increased risk of substance use disorder, with high responder rats showing quicker acquisition of drug self-administration and consumption compared to low responders. However, the high responder trait does not necessarily confer higher addiction behavior, but may require intermittent drug intake to actuate. This trait by state interaction produces a strong addiction-like phenotype in rats.
Article
Biochemistry & Molecular Biology
Subramaniam Jayanthi, Bruce Ladenheim, Patricia Sullivan, Michael T. McCoy, Irina N. Krasnova, David S. Goldstein, Jean Lud Cadet
Summary: Perturbations in striatal dopamine homeostasis may contribute to METH use disorder. Rats exposed to footshocks after long-term METH intake showed decreased intake when given a DA D1 receptor antagonist. Compulsive METH takers exhibited abnormal DA metabolism and decreased protein levels. These findings are consistent with studies on human METH users.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Jillian J. Weeks, Anthony A. Grace, Alan F. Sved
Summary: The study showed that both acute and chronic administration of nicotine improved deficits in schizophrenia-like behaviors and normalized neuronal activity in specific brain regions in the schizophrenia rodent model. These findings support the self-medication hypothesis for smoking in schizophrenia and suggest the potential of nicotinic modulation in future pharmacotherapies.
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Neurosciences
Rong-Rong Hu, Meng-Die Yang, Xiao-Yan Ding, Ning Wu, Jin Li, Rui Song
Summary: Opioid use disorder is a global public health challenge and effective medications for its management are lacking. The dopamine D-3 receptor antagonist YQA14 showed potential in reducing opioid self-administration and drug-seeking behavior in animal models. It also attenuated morphine-induced conditioned place preference and facilitated the extinguishing process. These findings suggest that the D-3 receptor plays a significant role in opioid addiction and YQA14 may have pharmacotherapeutic potential in attenuating opioid-induced addictive behaviors.
NEUROSCIENCE BULLETIN
(2023)
Article
Pharmacology & Pharmacy
Eleanor Blair Towers, Ivy L. Williams, Emaan I. Qillawala, Wendy J. Lynch
Summary: A hallmark of cocaine use disorder is dysfunction of dopamine signaling, particularly impaired D2 receptor signaling. Previous studies have mainly focused on males and found decreased D2 receptor binding in individuals with substance use disorder. However, this may not apply to females. This study aimed to assess sex differences in the role of D2 receptors in motivating cocaine use. Results showed that males, but not females, became less sensitive to D2 receptor antagonism with the development of an addiction-like phenotype.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Computer Science, Artificial Intelligence
Shivam Kalhan, Marta I. Garrido, Robert Hester, A. David Redish
Summary: Dysfunction in learning and motivational systems is believed to contribute to addictive behaviors. Previous models have limitations in explaining the key features of addictive behaviors, but this study proposes a novel mathematical model that combines dopamine's role in learning and motivation to simulate addictive behaviors accurately. The model also explains some key characteristics of addictive behaviors.
Article
Chemistry, Medicinal
Anjela Manandhar, Benjamin E. Blass, Dennis J. Colussi, Imane Almi, Magid Abou-Gharbia, Michael L. Klein, Khaled M. Elokely
Summary: The global population is currently facing a COVID-19 pandemic caused by SARS-CoV-2, with researchers exploring potential vaccines and treatments. The proteinase M3CLpro is being studied as a promising drug target, with investigations into its dynamic changes upon ligand binding using X-ray crystal structures. This research aims to aid in the design of potent protease inhibitors to combat the ongoing pandemic.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Biology
Michela Dell'Orco, Amir Elyaderani, Annika Vannan, Shobana Sekar, Gregory Powell, Winnie S. Liang, Janet L. Neisewander, Nora Perrone-Bizzozero
Summary: The RNA-binding protein HuD plays a critical role in brain development, neurodegenerative diseases, and substance use disorders by regulating coding and non-coding RNA networks associated with neuronal differentiation and synaptic physiology.
Article
Chemistry, Medicinal
Nicky Hwang, Haiqun Ban, Shuo Wu, Kelly McGuire, Ellen Hernandez, Junjun Chen, Qiong Zhao, Manasa Suresh, Benjamin Blass, Usha Viswanathan, John Kulp, Jinhong Chang, Jason Clement, Stephan Menne, Ju-Tao Guo, Yanming Du
Summary: HBV core protein is a key component of the HBV capsid and plays various roles in viral replication. This study identified a new benzamide compound with improved metabolic stability and good bioavailability, making it a potential candidate for the development of antiviral agents targeting HBV capsid assembly.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Neurosciences
Thomas Oh, Elyas S. Daadi, Jeffrey Kim, Etienne W. Daadi, Peng-Jen Chen, Gourav Roy-Choudhury, Jonathan Bohmann, Benjamin E. Blass, Marcel M. Daadi
Summary: Parkinson's disease is a complex multisystem chronic disease for which levodopa is the main pharmacotherapy, but it often leads to levodopa-induced dyskinesia within 5 years. A new small molecule compound PD13R has been discovered to eliminate levodopa-induced dyskinesia and improve PD symptoms. Further studies are focused on developing PD13R as a treatment for PD patients with dyskinesia.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Chemistry, Medicinal
Benjamin E. Blass, Rong Gao, Kevin M. Blattner, John C. Gordon, Douglas A. Pippin, Daniel J. Canney
Summary: The sigma-2 receptor has been found to be associated with various diseases, and is currently being investigated as a therapeutic target. This study reports the synthesis and evaluation of a series of novel sigma-2 receptor ligands, which exhibit high potency.
MEDICINAL CHEMISTRY RESEARCH
(2022)
Article
Chemistry, Medicinal
Benjamin E. Blass, Peng-Jen Chen, Michelle Taylor, Suzy A. Griffin, John C. Gordon, Robert R. Luedtke
Summary: Substance use disorder, particularly with cocaine, is a significant medical need with no approved therapies. The D3 dopamine receptor has been identified as a potential treatment target, and a new series of compounds with higher solubility and selectivity for D-3 has been discovered.
MEDICINAL CHEMISTRY RESEARCH
(2022)
Article
Chemistry, Medicinal
Benjamin E. Blass, Peng-Jen Chen, Michelle Taylor, Suzy A. Griffin, John C. Gordon, Robert R. Luedtke
Summary: Dopamine is a neurotransmitter linked to various diseases. This study reports a series of novel D-3 ligands with improved solubility compared to previous compounds.
MEDICINAL CHEMISTRY RESEARCH
(2022)
Article
Chemistry, Medicinal
Benjamin E. Blass, Richie Rashmin Bhandare, Daniel J. Canney
Summary: The sigma-2 receptor is associated with various diseases, and we have identified a series of novel sigma(2) ligands, one of which has high affinity and selectivity.
MEDICINAL CHEMISTRY RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Qiangnan Zhang, Thomas Durig, Benjamin Blass, Reza Fassihi
Summary: This research presents the development of a sustained-release drug delivery system based on amorphous solid dispersion (ASD) for Apremilast. The designed SR tablet matrices exhibited gradual dissolution and release of over 90% of the drug over 15-20 hours, indicating its potential for once-daily administration and improved bioavailability. The ASD formulation increased the solubility and dissolution rate of Apremilast, and prevented recrystallization or polymorphic interconversion.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Chemistry, Medicinal
Benjamin E. Blass, Peng-Jen Chen, Michelle Taylor, Suzy A. Griffin, John C. Gordon, Robert R. Luedtke
Summary: Dopamine plays a crucial role in both the central nervous system and the periphery, exerting its physiological effects through interaction with G-protein-coupled receptors. Abnormal D-3 activity has been associated with various diseases and conditions, and a novel high affinity ligand for D-3 receptor has been identified.
MEDICINAL CHEMISTRY RESEARCH
(2022)
Article
Chemistry, Medicinal
Benjamin E. Blass, Peng-Jen Chen, John C. Gordon
Summary: Cocaine use disorder is a significant medical need without approved pharmacotherapies. The D3 dopamine receptor is a potential therapeutic target under investigation for addressing this issue.
MEDICINAL CHEMISTRY RESEARCH
(2022)
Article
Chemistry, Medicinal
Benjamin E. Blass, Kevin M. Blattner, John C. Gordon, Khaled M. Elokely, Douglas A. Pippin, Daniel J. Canney
Summary: The sigma-2 receptor, known as TMEM97 or MAC30, is associated with various diseases and conditions. This study focused on the evaluation of a series of novel compounds for their sigma(1)/sigma(2) selectivity and ADME properties through in vitro assays. The findings contribute to the potential discovery of new therapeutic approaches for sigma-2 receptor-related diseases.
MEDICINAL CHEMISTRY RESEARCH
(2022)
Article
Neurosciences
Anaissa Ruiz-Tejada, Janet Neisewander, Christos S. Katsanos
Summary: Physical activity is beneficial for health, but only a small number of adults engage in regular physical activity. Further research is needed to understand the biological mechanisms of motivation and habit formation to enhance physical activity levels.
Article
Public, Environmental & Occupational Health
Alvaro Aguilar-Setien, Nidia Arechiga-Ceballos, Gary A. Balsamo, Amy J. Behrman, Hannah K. Frank, Gary R. Fujimoto, Elizabeth Gilman Duane, Thomas Warner Hudson, Shelley M. Jones, Luis A. Ochoa Carrera, Gregory L. Powell, Carrie A. Smith, Joni Triantis Van Sickle, Susan E. Vleck
Summary: This article focuses on the considerations for conducting field work with bats, addressing risk assessment, occupational health, and biosafety concerns. It emphasizes the need to address legal and ethical issues in the planning process and provides recommendations for safely conducting field work to protect both researchers and animals.
Article
Public, Environmental & Occupational Health
Erin Lauer, Kelly N. Kim, Robert A. Dettmann, Adam E. J. Fleming, Gregory L. Powell, Amanda D. Rice, Giorgio Scarpellini, Rocco Casagrande, David R. Gillum
Summary: Arthropods are important vectors for disease transmission, and research into vector-borne diseases is crucial for public health. Insectary facilities are essential for safe handling of arthropod-borne hazards. Arizona State University faced delays in constructing their ACL-3 insectary, but valuable lessons were learned for future projects.
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
(2023)