Article
Pharmacology & Pharmacy
Yawei Xu, Yalei Ning, Yan Zhao, Yan Peng, Fen Luo, Yuanguo Zhou, Ping Li
Summary: Caffeine as a nonspecific antagonist of the adenosine A(2A) receptor enhances learning and memory function while also correlating with feelings of anxiety. The differential effects of inhibiting A(2A)Rs in the dorsal and ventral hippocampus lead to enhanced memory and increased anxiety, respectively. Optogenetic activation of dorsal or ventral hippocampal A(2A)Rs can reverse these behavioral alterations caused by caffeine intake.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Clinical Neurology
Ornella Valenti, Alice Zambon, Stefan Boehm
Summary: The study found that a single dose of amphetamine and the selective adenosine A2A antagonist KW-6002 reduced population activity of dopamine neurons, while repeated administration led to drug-conditioned place preference and unaltered or enhanced activity. Conversely, recurring injections of caffeine or DPCPX did not cause conditioned place preference and consistently reduced dopamine neuron activity.
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Kathrine Louise Jensen, Soren Brogger Jensen, Kenneth Lindegaard Madsen
Summary: Psychostimulant use disorder is a major global health issue with no effective pharmacological treatments available. This review provides an overview of pharmacological treatments targeting different aspects of psychostimulant addiction, including the dopamine system, the glutamate system, and the severe side effects of quitting long-term use. Promising results have been found with drugs modulating the dopamine system, cognitive enhancers, and drugs targeting the glutamate system, but further research is needed for sufficient evidence of efficacy and tolerability.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Brandon M. Fritz, Fuqin Yin, Brady K. Atwood
Summary: The medial and lateral dorsal striatum play different roles in driving goal-directed and habitual/compulsive behaviors, respectively. Adenosine A(1) receptors in the dorsal striatum regulate excitatory glutamate transmission, potentially influencing striatally-mediated behaviors. The study found that activation of presynaptic A1Rs led to synaptic depression in both DLS and DMS, suggesting a potential role of A1Rs in neuropsychiatric diseases.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Veronica Rivi, Cristina Benatti, Joan M. C. Blom, Luca Pani, Nicoletta Brunello, Filippo Drago, Francesco Papaleo, Filippo Caraci, Federica Geraci, Sebastiano Alfio Torrisi, Gian Marco Leggio, Fabio Tascedda
Summary: Cognitive impairment in schizophrenia is a challenging problem that hasn't been solved clinically or pharmacologically. Dysfunctional dysbindin and dopamine receptor D3 have been found to improve cognitive functions, but the underlying molecular mechanisms are not fully understood.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Saeideh Karimi-haghighi, Maedeh Mahmoudi, Fatemeh Sayehmiri, Roghayeh Mozafari, Abbas Haghparast
Summary: The mechanism behind relapse in addiction treatment with psychostimulant drugs is not fully understood, and there is conflicting evidence regarding the role of the endocannabinoid system in regulating relapse in preclinical studies. This systematic review evaluated the effect of endocannabinoid modulators on the reinstatement of commonly abused psychostimulants. Thirty-nine articles using different animal models were selected, and the results suggest that cannabinoid receptor antagonists and agonists may have potential in inhibiting the reinstatement of cocaine and methamphetamine addiction, but the effectiveness depends on time, dose, and route of administration.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Behavioral Sciences
Kyna-Anne Conn, Suzy Alexander, Thomas H. J. Burne, James P. Kesby
Summary: This study examines the role of D1 and D2 receptors in learning induced by amphetamine. The results suggest that overall D1 receptor availability is crucial for learning, while modifying D2 receptor function can ameliorate learning deficits in a state of elevated dopamine.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Review
Behavioral Sciences
E. Theresa Bjorness, W. Robert Greene
Summary: Dopamine, orexin, and adenosine systems play dual roles in reward and sleep/arousal. Drug abuse may influence both reward and sleep/arousal mechanisms. Cocaine can cause acute sleep loss and abnormal recovery patterns under chronic exposure conditions. Experimentally induced sleep disturbance may increase cocaine seeking behavior.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2021)
Review
Neurosciences
Melinda Hersey, Amanda K. Bacon, Lydia G. Bailey, Mark A. Coggiano, Amy H. Newman, Lorenzo Leggio, Gianluigi Tanda
Summary: The rapid increase in individuals affected by psychostimulant use disorder (PSUD) has highlighted the potential of Modafinil (MOD) as a therapeutic option due to its non-addictive properties, despite its similar mechanism of action to commonly abused psychostimulants on the dopamine transporter (DAT). Clinical and preclinical studies have demonstrated the efficacy of MOD in treating symptoms related to PSUD and other psychiatric disorders involving alterations of brain dopamine systems.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Substance Abuse
Colleen Synan, Carrie Bowen, David J. Heal, Christelle Froger-Colleaux, Patrick M. Beardsley, Nina Dedic, Seth C. Hopkins, Una Campbell, Kenneth S. Koblan
Summary: Ulotaront, a novel drug for the treatment of schizophrenia, was found to have no abuse potential in rats and may have therapeutic utility in substance use disorders.
DRUG AND ALCOHOL DEPENDENCE
(2022)
Review
Neurosciences
Ana Moreira-de-Sa, Vanessa S. Lourenco, Paula M. Canas, Rodrigo A. Cunha
Summary: Extracellular adenosine serves as a paracrine signal of cellular effort produced during increased metabolic activity or stress. Adenosine receptors, particularly A(2A) receptors, play a significant role in promoting physiological changes in brain function. Overactivation of A(2A) receptors may contribute to synaptic and neuronal damage, and could be an early indicator of brain disease progression.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Muhammad O. Chohan, Hannah Yueh, Halli Fein, Jared M. Kopelman, Susanne E. Ahmari, Jeremy Veenstra-VanderWeele
Summary: Repeated amphetamine use leads to locomotor sensitization, which may be related to the development of psychosis and addiction. The interaction between dopaminergic and glutamatergic systems plays a significant role in amphetamine sensitization. However, the impact of chronic alterations in the expression of the excitatory amino acid transporter (EAAT3) on this phenomenon is still uncertain.
NEUROCHEMISTRY INTERNATIONAL
(2022)
Article
Behavioral Sciences
Sara Floren Lind, Frida Stam, Sofia Zelleroth, Evelina Meurling, Andreas Frick, Alfhild Gronbladh
Summary: Caffeine has anxiogenic effects on rats with high anxiety-like behavior, reducing their risk-taking behavior and causing a decrease in adenosine A2A receptor mRNA expression in the caudate putamen and an increase in BDNF expression in the hippocampus. These results suggest that the effects of caffeine on individuals may vary depending on their baseline anxiety-like behavior and highlight the importance of adenosine receptors as a potential drug target for anxiety disorders.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2023)
Article
Medicine, Research & Experimental
Phillip M. Mackie, Adithya Gopinath, Dominic M. Montas, Alyssa Nielsen, Aidan Smith, Rachel A. Nolan, Kaitlyn Runner, Stephanie M. Matt, John McNamee, Joshua E. Riklan, Kengo Adachi, Andria Doty, Adolfo Ramirez-Zamora, Long Yan, Peter J. Gaskill, Wolfgang J. Streit, Michael S. Okun, Habibeh Khoshbouei
Summary: Monocyte-derived macrophages play crucial roles in tissue homeostasis and diseases, regulated by various signaling molecules. Recent studies have shown the ability of biogenic amines to control macrophage functions, with a focus on the mechanisms surrounding immune cells remaining unclear. Investigating the functions of norepinephrine transporter (NET) and dopamine transporter (DAT) on human MDMs, researchers found that DAT may play a potential role in regulating innate immunity through an immunomodulatory mechanism mediated by LPS-induced dopamine reverse transport.
Review
Pharmacology & Pharmacy
Daniel C. Javitt
Summary: Cognitive impairment is a prominent feature of schizophrenia, and its assessment methods are well established. The role of social cognitive impairment and sensory-level dysfunction in functional outcomes has also been recognized. Treatment development targeting N-methyl-d-aspartate receptor (NMDAR) and its associated impairments has become encouraging. Mismatch negativity has emerged as a promising biomarker for early-stage drug development in schizophrenia.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
(2023)
Article
Biochemical Research Methods
Tao Xu, Jingu Wang, Bingjie Hu, Guosi Zhang, Wu Zhou, Meiqin Zheng, Bo Shen, Baochang Sun, Yanjun Zhang, Yin Chen, Jian Yu, Min Liang, Jingye Pan, Chengshui Chen, Haixiao Chen, Minghua Jiang, Liangde Xu, Jia Qu, Jiang-Fan Chen
Summary: The development of an anchor primer-based assay targeting the N gene and RNase has improved the stability and sensitivity of SARS-CoV-2 RNA detection. This method can detect viral RNA in various samples, aiding in the identification of viral carriage in COVID-19 patients.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Zhanglei Dong, Bingwu Huang, Chenchen Jiang, Jiangfan Chen, Han Lin, Qingquan Lian, Binbin Wu
Summary: This study provides evidence that NAc A2AR activation suppresses cue-induced propofol relapse in rats through interacting with D2R. Focal knockdown of A2AR did not affect the acquisition of propofol self-administration behavior, but enhanced cue-induced reinstatement. Pharmacological activation of A2AR or blockade of D2R attenuated propofol seeking behavior.
NEUROCHEMICAL RESEARCH
(2021)
Article
Immunology
Wu Zheng, Yijia Feng, Zhenhai Zeng, Mengqian Ye, Mengru Wang, Xin Liu, Ping Tang, Huiping Shang, Xiaoting Sun, Xiangxiang Lin, Muran Wang, Zhengzheng Li, Yiyun Weng, Wei Guo, Sergii Vakal, Jiang-fan Chen
Summary: A(2A)R is upregulated in the choroid plexus (CP), enhancing its gateway activity in experimental autoimmune encephalomyelitis (EAE) mice. Treatment with the A(2A)R antagonist KW6002 reduces T cell trafficking across the CP and attenuates EAE pathology. Focal knock-down of CP-A(2A)R inhibits the infiltration of Th17(+) cells across the CP through the CCR6-CCL20 axis, leading to protection against EAE pathology. Activation of A(2A)R in the cultured CP epithelium increases CP permeability and facilitates lymphocyte migration.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Immunology
Qiang Xiao, Xu Han, Gaoyu Liu, Dongmei Zhou, Lijuan Zhang, Juan He, Haixu Xu, Pan Zhou, Quan Yang, Jiangfan Chen, Jie Zhou, Guanmin Jiang, Zhi Yao
Summary: Adenosine signaling through A2A receptor negatively regulates ILC2s and allergic airway inflammation, providing protection against airway inflammation and representing a potential therapeutic target for controlling asthma.
MUCOSAL IMMUNOLOGY
(2022)
Correction
Immunology
Qiang Xiao, Xu Han, Gaoyu Liu, Dongmei Zhou, Lijuan Zhang, Juan He, Haixu Xu, Pan Zhou, Quan Yang, Jiangfan Chen, Jie Zhou, Guanmin Jiang, Zhi Yao
MUCOSAL IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mengqian Ye, Mengru Wang, Yijia Feng, Huiping Shang, Yuwen Yang, Lanxin Hu, Muran Wang, Serhii Vakal, Xiangxiang Lin, Jiangfan Chen, Wu Zheng
Summary: The choroid plexus is a key gateway for peripheral immune cells to enter the CNS. The activity of this gateway is regulated by adenosine A(2A) receptor (A(2A)R) signaling. A(2A)R activity also influences CP permeability and immune homeostasis in the CNS.
PURINERGIC SIGNALLING
(2023)
Article
Neurosciences
Zhu Lin, Feng You, Ting Li, Yijia Feng, Xinyue Zhao, Jingjing Yang, Zhimo Yao, Ying Gao, Jiang-Fan Chen
Summary: Recent studies have shown that astrocytes in the hippocampus exhibit calcium dynamics regulated by sensory inputs and reward delivery, with synchronized but phase-differing dynamics compared to neurons. Additionally, robust synchronization of astrocytic calcium dynamics at the population level was observed among the hippocampus, medial prefrontal cortex, and striatum. The inter-locked, bidirectional communication between astrocytes and neurons may play a role in modulating information processing in working memory.
NEUROSCIENCE BULLETIN
(2022)
Review
Biochemistry & Molecular Biology
Akihisa Mori, Jiang-Fan Chen, Shinichi Uchida, Cecile Durlach, Shelby M. King, Peter Jenner
Summary: Adenosine A(2A) receptor antagonists are considered as pharmacological targets for treating Parkinson's disease and have the potential to address both motor and non-motor symptoms, as well as modify the disease itself.
Article
Neurosciences
Gengjing Fang, Yuling Zhou, Xiaopeng Zhou, Hui Zhou, Yuan-Yuan Ge, Shengtao Luo, Jiang-Fan Chen, Liping Zhang
Summary: The study revealed that A(2A)R antagonist KW6002 partially reversed CCCP-induced retinal injury by increasing mitochondrial content and reducing cell apoptosis. Transcriptome sequencing showed that A(2A)R blockade decreased the number of CCCP-induced microRNAs by 60% and increased circular RNAs by 50%. These findings provide insights into the neuroprotective mechanisms of A(2A)R antagonists against CCCP-induced retinal injury.
Review
Pharmacology & Pharmacy
Hao-Yun Luo, Hai-Ying Shen, R. Serene Perkins, Ya-Xu Wang
Summary: Methylation is an important mechanism in cancer pathology, and the adenosine metabolic clearance enzyme ADK plays a role in regulating tumor suppressor gene methylation and tumor development. Targeting DNA methylation of cancer-related genes is a promising therapeutic strategy, but current drugs have side effects, highlighting the need for safer and more specific inhibitors.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Hai-Ying Shen, Sadie B. Baer, Raey Gesese, John M. Cook, Landen Weltha, Shayla Q. Coffman, Jie Wu, Jiang-Fan Chen, Ming Gao, Teng Ji
Summary: This study aimed to evaluate the role of adenosine A(2A) receptor (A(2A)R) in the development of a SUDEP mouse model. The researchers found that the level of A(2A)R in the nucleus tractus solitarius (NTS) was increased in epileptic mice and that inhibiting A(2A)R could reduce SUDEP events. The findings suggest that A(2A)R may be a potential therapeutic target for preventing SUDEP.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yevheniia Velihina, Raey Gesese, Victor Zhirnov, Oleksandr Kobzar, Benjamin Bui, Stepan Pilyo, Andriy Vovk, Hai-Ying Shen, Volodymyr Brovarets
Summary: A series of 1,3-oxazolo[4,5-d]pyrimidine and 1,3-oxazolo[5,4-d]pyrimidine derivatives were synthesized and tested against breast cancer cell lines. The compounds showed activity against most cell lines in the micromolar range and displayed correlation with tamoxifen and aclacinomycin A. Compound 1 effectively suppressed ADK in cultured MDA-MB 231 cell lines, suggesting it as a potential target for anticancer properties.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Neurosciences
Yan He, Linshan Huang, Ke Wang, Xinran Pan, Qionghui Cai, Feiyang Zhang, Jingjing Yang, Gengjing Fang, Xinyue Zhao, Feng You, Yijia Feng, Yan Li, Jiang-Fan Chen
Summary: This study investigates the behavioral mechanism of alpha-Syn in Parkinson's disease (PD) and suggests a novel therapeutic strategy to improve sequence-learning deficit by using adenosine A2A receptor antagonists.
Article
Ophthalmology
Guodong Liu, Hui Li, Grant Cull, Laura Wilsey, Hongli Yang, Jesica Reemmer, Hai-Ying Shen, Fang Wang, Brad Fortune, Bang V. Bui, Lin Wang
Summary: The downregulation of retinal Cx43 compromises vasoreactivity of both arterioles and venules in response to an OPP decrease, suggesting that Cx43-mediated glial communication actively regulates resting venular diameter.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
