Article
Biochemistry & Molecular Biology
Yasumi Ohta, Takaaki E. Murakami, Mamiko Kawahara, Makito Haruta, Hironari Takehara, Hiroyuki Tashiro, Kiyotaka Sasagawa, Jun Ohta, Metin Akay, Yasemin M. Akay
Summary: This study confirms the importance of dopamine in reward behavior, as well as the interaction between dopaminergic and GABAergic neurons. The researchers used optogenetics to stimulate neurons in mice and measured dopamine release. The results show that different stimulation frequencies have different effects on dopamine release, and GABAergic neurons have an inhibitory effect on dopamine activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Yuxiao Mei, Qi-Wei Zhang, Qingyi Gu, Zhichao Liu, Xiao He, Yang Tian
Summary: This article describes a new supramolecular fluorescent probe that efficiently identifies largescale neurotransmitters and enables high-throughput analysis using principal component analysis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Young Woo Noh, Yangsik Kim, Soowon Lee, Yeonghyeon Kim, Jae Jin Shin, Hyojin Kang, Il Hwan Kim, Eunjoon Kim
Summary: Dopamine neurons in the ventral tegmental area (VTA) communicate with cortical neurons through the medial prefrontal cortex (mPFC)-lateral hypothalamus (LH)-VTA pathway. This pathway plays a crucial role in regulating social deficits in mice with IRSp53 deletion. The deletion leads to abnormal excitability in LH-projecting mutant mPFC neurons, resulting in excessive excitatory synaptic input to LH-GABA neurons. This disrupts the inhibitory LHGABA-VTAGABA pathway, leading to social deficits.
MOLECULAR PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Han Guo, Jian-Bo Jiang, Wei Xu, Mu-Tian Zhang, Hui Chen, Huan-Ying Shi, Lu Wang, Miao He, Michael Lazarus, Shan-Qun Li, Zhi-Li Huang, Wei-Min Qu
Summary: In this study, the authors found that neurons expressing calretinin in the parasubthalamic nucleus play a key role in the induction and maintenance of wakefulness associated with exploration. They demonstrate that these neurons regulate wakefulness by innervating the ventral tegmental area. These findings provide new insights into the neural circuits regulating wakefulness.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Arnaud L. Lalive, Mauro Congiu, Christopher Lewis, Dominik Groos, Joseph A. Clerke, Anna Tchenio, Yuan Ge, Fritjof Helmchen, Manuel Mameli
Summary: Through experiments with mice, it was found that the activity of lateral habenula neurons decreases with the decrease of reward-related stimuli, and this phenomenon can guide reward-driven behavior through synaptic inhibition.
Article
Multidisciplinary Sciences
Xiaoting Wu, Wade Morishita, Kevin T. Beier, Boris D. Heifets, Robert C. Malenka
Summary: This study identifies the medial septum as a critical input region for social memory formation and demonstrates that serotonin modulation in the medial septum plays a bidirectional role in controlling the stability of social memories.
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
Biochemistry & Molecular Biology
Laura A. Struzyna, Kevin D. Browne, Justin C. Burrell, Wisberty J. Gordian Velez, Kathryn L. Wofford, Hilton M. Kaplan, N. Sanjeeva Murthy, H. Isaac Chen, John E. Duda, Rodrigo A. Espana, D. Kacy Cullen
Summary: This study successfully created a tissue-engineered nigrostriatal pathway (TE-NSP) using microtissue engineering techniques. The implanted TE-NSP showed survival, dopamine release, and integration with host tissue in a rat PD model, providing a potential strategy for replacing lost neuroarchitecture in PD patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Vishnu Raj, Anoopkumar Thekkuveettil
Summary: This study elucidates the critical role of dopamine in the memory pathway, using Caenorhabditis elegans as a model. It also highlights the significance of dopaminergic neurons in adaptive learning and memory.
JOURNAL OF NEUROSCIENCE RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Ya-Dong Li, Yan-Jia Luo, Wei Xu, Jing Ge, Yoan Cherasse, Yi-Qun Wang, Michael Lazarus, Wei-Min Qu, Zhi-Li Huang
Summary: VP GABAergic neurons play a crucial role in regulating arousal by modulating dopaminergic neurons and promoting wakefulness. Additionally, they promote arousal through innervation of the lateral hypothalamus, but do not affect depression-like behaviors or food intake.
MOLECULAR PSYCHIATRY
(2021)
Review
Cell Biology
Bradley M. Roberts, Emanuel F. Lopes, Stephanie J. Cragg
Summary: Striatal dopamine release is inhibited by striatal gamma-aminobutyric acid (GABA) acting via GABA(A) and GABA(B) receptors, which is regulated by plasma membrane GABA uptake transporters on striatal astrocytes. The regulation of striatal GABA-DA interactions serves as a potential therapeutic target for psychomotor disorders associated with dysregulated DA signaling.
Article
Multidisciplinary Sciences
Clement Solie, Alessandro Contestabile, Pedro Espinosa, Stefano Musardo, Sebastiano Bariselli, Chieko Huber, Alan Carleton, Camilla Bellone
Summary: This study shows that the pathway from superior colliculus to ventral tegmental area (VTA) plays a key role in encoding orienting behavior and modulating social interaction. The researchers found that this pathway affects VTA dopamine neurons projecting onto dorsolateral striatum, and the stimulation or inhibition of this pathway can influence social interaction in mice.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Gyorgy Szabo, Oliver Elias, Peter Erdelyi, Attila Potor, Gyorgy I. . Turos, Benedek I. Karolyi, Gabor Varro, Agnes Gy. Vasko, Imre Bata, Gabor L. Kapus, Zoltan Dohanyos, Amrita A. . Bobok, Laszlo Fodor, Marta Than, Monika Vastag, Zsolt Komlodi, Soukupne Rita E. Kedves, Eva Mako, Brigitta Suveges, Greiner Istvan
Summary: This study discloses the discovery and characterization of novel naphthyridine derivatives with selective alpha 5-GABA(A)R negative allosteric modulator (NAM) activity. By utilizing a scaffold-hopping strategy, fused [6 + 6] bicyclic scaffolds were designed and synthesized. Among these, 1,6-naphthyridinones were identified as potent and selective alpha 5-GABA(A)R NAMs with improved profile. Compound 20, with the most balanced profile, demonstrated in vivo proof of concept (POC) for the new scaffold in animal models of cognitive impairment associated with schizophrenia (CIAS).
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Cell Biology
Robert A. Phillips, Jennifer J. Tuscher, Samantha L. Black, Emma Andraka, N. Dalton Fitzgerald, Lara Ianov, Jeremy J. Day
Summary: This study comprehensively defines the molecular architecture of the ventral tegmental area (VTA) by performing single-nucleus RNA sequencing on rat VTA cells. It identifies selective markers for dopamine and combinatorial neurons, reveals expression profiles for drug receptors, and demonstrates population-specific enrichment of gene sets linked to brain disorders.
Article
Biochemistry & Molecular Biology
Yanlin He, Xing Cai, Hailan Liu, Krisitine M. Conde, Pingwen Xu, Yongxiang Li, Chunmei Wang, Meng Yu, Yang He, Hesong Liu, Chen Liang, Tingting Yang, Yongjie Yang, Kaifan Yu, Julia Wang, Rong Zheng, Feng Liu, Zheng Sun, Lora Heisler, Qi Wu, Qingchun Tong, Canjun Zhu, Gang Shu, Yong Xu
Summary: The translation discusses how obesity is primarily caused by consuming excessive calories beyond energetic requirements, while the underlying drivers have not been fully defined. The study found that activating specific neural pathways can regulate different types of feeding behavior, driven by either hunger or non-hunger cues.
MOLECULAR PSYCHIATRY
(2021)
Article
Immunology
Chiomah Ezeomah, Kathryn A. Cunningham, Sonja J. Stutz, Robert G. Fox, Natalya Bukreyeva, Kelly T. Dineley, Slobodan Paessler, Irma E. Cisneros
BRAIN BEHAVIOR AND IMMUNITY
(2020)
Article
Neurosciences
Dennis J. Sholler, Christina R. Merritt, Brionna D. Davis-Reyes, George Golovko, Noelle C. Anastasio, Kathryn A. Cunningham
Article
Neurosciences
Irma E. Cisneros, Kathryn A. Cunningham
NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Substance Abuse
Kabir B. Nigam, Lisa K. Straub, Edward A. Zuniga, Aysha Sami, Kathryn A. Cunningham, Noelle C. Anastasio, F. Gerard Moeller, James M. Bjork
Summary: This study investigated the neural circuit characteristics and effects of behavioral control in patients with cocaine use disorder, revealing attenuated covert features of attention and proactive control in these patients, which may partially account for their susceptibility to relapse due to poor executive function.
DRUG AND ALCOHOL DEPENDENCE
(2021)
Review
Pharmacology & Pharmacy
Nicholas M. Barnes, Gerard P. Ahern, Carine Becamel, Joel Bockaert, Michael Camilleri, Severine Chaumont-Dubel, Sylvie Claeysen, Kathryn A. Cunningham, Kevin C. Fone, Michael Gershon, Giuseppe Di Giovanni, Nathalie M. Goodfellow, Adam L. Halberstadt, Rachel M. Hartley, Gherici Hassaine, Katharine Herrick-Davis, Ruud Hovius, Enza Lacivita, Evelyn K. Lambe, Marcello Leopoldo, Finn Olav Levy, Sarah C. R. Lummis, Philippe Marin, Luc Maroteaux, Andrew C. McCreary, David L. Nelson, John F. Neumaier, Adrian Newman-Tancredi, Hugues Nury, Alexander Roberts, Bryan L. Roth, Anne Roumier, Gareth J. Sanger, Milt Teitler, Trevor Sharp, Carlos M. Villalon, Horst Vogel, Stephanie W. Watts, Daniel Hoyer
Summary: This review provides a comprehensive account of the classification and function of 5-hydroxytryptamine receptors, including how they are targeted for therapeutic benefit.
PHARMACOLOGICAL REVIEWS
(2021)
Article
Behavioral Sciences
Brionna D. Davis-Reyes, Ashley E. Smith, Jimin Xu, Kathryn A. Cunningham, Jia Zhou, Noelle C. Anastasio
Summary: The concept of impulse control, originating from early psychiatry, has evolved into a multidimensional endophenotype underlying various neuropsychiatric disorders. Evidence suggests that dysfunction in glutamate neurotransmission drives cognitive and behavioral aspects of impulsivity. Pharmacological approaches targeting GluR signaling, such as ketamine and AMPAR positive allosteric modulation, may effectively normalize impulsivity and improve neuropsychiatric disorders characterized by aberrant impulse control.
BEHAVIOURAL PHARMACOLOGY
(2021)
Article
Neurosciences
Caitlin R. Schlagal, Tiffany J. Dunn, Pei Xu, Daniel E. Felsing, Christina R. Merritt, Sanjana Manja, Robert G. Fox, Shelly A. Buffington, George Saade, Kelly T. Dineley, Yongjia Yu, Kathryn A. Cunningham, Ping Wu
Summary: The use of opioids by pregnant women has increased significantly since 2004, leading to a rise in neonatal opioid withdrawal syndrome (NOWS) and other neurological deficits in offspring. A novel mouse model was developed to study the consequences of maternal opioid use on fetal neurodevelopment, revealing critical changes in brain development and behavioral anomalies in adolescent offspring. These findings suggest a teratogenic effect of prenatal opioid exposure.
Article
Psychiatry
Sade E. Johns, Lori Keyser-Marcus, Antonio Abbate, Edward Boone, Benjamin Van Tassell, Kathryn A. Cunningham, Noelle C. Anastasio, Justin L. Poklis, Tatiana Ramey, F. Gerard Moeller
Summary: The study demonstrated the safety of administering the 5-HT2CR agonist lorcaserin with cocaine in patients with CocUD, but it showed a lack of efficacy in reducing the reinforcing effects of cocaine. This suggests a disconnect between the effects of 5-HT2CR agonists on craving and cocaine choice in human cocaine users.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Neurosciences
I. E. Cisneros, K. A. Cunningham
Summary: The Covid-19 pandemic has exacerbated the drug overdose and substance use disorder epidemic, with social isolation, economic distress, and mental health issues disproportionally affecting vulnerable populations, potentially leading to instability in central nervous system functioning and the development of neuropsychiatric symptoms.
Article
Neurosciences
James M. Kasper, Ashley E. Smith, Sierra N. Miller, Ara, William K. Russell, Kathryn A. Cunningham, Jonathan D. Hommel
Summary: The neurotransmitter neuromedin U (NMU) and its receptor were found to regulate motivation for cocaine, affecting GABA release and c-Fos expression, leading to reduced breakpoints for cocaine. Using viral transsynaptic studies, it was discovered that NMU impacts the GABAergic pathway from the dorsal raphe nucleus to the nucleus accumbens shell to the ventral pallidum. These findings advance understanding of the neurochemical regulation of pathways specific to cocaine self-administration.
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Cell Biology
Eun-Seon Yoo, Li Li, Lin Jia, Caleb C. Lord, Charlotte E. Lee, Shari G. Birnbaum, Claudia R. Vianna, Eric D. Berglund, Kathryn A. Cunningham, Yong Xu, Jong-Woo Sohn, Chen Liu
Summary: The study shows that Htr2c in Sim1 neurons plays a role in promoting food intake and counteracting the effects of serotonergic appetite suppressants. Moreover, activation of PVH Htr2c suppresses hunger while inhibition promotes feeding.
Meeting Abstract
Biochemistry & Molecular Biology
Leah M. Salinsky, Robert Fox, Noelle Anastasio, Kathryn A. Cunningham
Article
Psychiatry
Liangsuo Ma, Kathryn A. Cunningham, Noelle C. Anastasio, James M. Bjork, Brian A. Taylor, Albert J. Arias, Brien P. Riley, Andrew D. Snyder, F. Gerard Moeller
Summary: Patients with Cocaine Use Disorder (CUD) exhibit diverse symptoms and unpredictable responses to treatment, emphasizing the importance of identifying biobehavioral signatures to predict success in clinical trials. This study utilized a task-based behavioral and pharmacogenetic-fMRI approach to investigate craving and attentional bias in CUD patients. The findings suggest that the wild-type 5-HT2CR gene is necessary for the efficacy of the serotonin antagonist mirtazapine in reducing activated effective connectivity in CUD patients.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Pharmacology & Pharmacy
Christina R. Merritt, Irma E. Cisneros, Obdulia Covarrubias-Zambrano, Sonja J. Stutz, Massoud Motamedi, Stefan H. Bossmann, Kathryn A. Cunningham
Summary: This article discusses the challenges physicians face in treating pain patients and highlights the lack of quantifiable, objective methods of measuring pain in clinical settings. The study uses an animal model to investigate the relationship between circulating regulators of the inflammatory response and objective behavioral responses to inflammatory pain. The findings suggest that certain cytokines and matrix metalloproteinases may serve as predictive biomarkers for inflammation-associated locomotor impairment.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Christina R. Merritt, Ashley E. Smith, Kamil Khanipov, George Golovko, Kelly T. Dineley, Noelle C. Anastasio, Kathryn A. Cunningham
Summary: The lack of FDA-approved medications for the treatment of cocaine use disorder (CUD) has contributed to the increase in drug overdose deaths involving cocaine. This study used next-generation sequencing to identify specific genes associated with cue-evoked cocaine-seeking behavior in the medial prefrontal cortex (mPFC) of rats. The findings provide potential candidates for future pharmacotherapeutics aimed at maintaining abstinence in CUD.
FRONTIERS IN PHARMACOLOGY
(2022)