Review
Biochemistry & Molecular Biology
Melinda Hersey, Mattingly K. Bartole, Claire S. Jones, Amy Hauck Newman, Gianluigi Tanda
Summary: Psychostimulant use disorders (PSUD) have significant public health and economic burdens, with sex differences observed in dependence onset, relapse rates, and treatment success. These differences may be related to neurochemical differences in the dopaminergic system, with females showing greater effects during the high estradiol phase. Women are more likely to start drug use at younger ages and exhibit higher desire for cocaine compared to men. Modafinil, a DAT inhibitor used for narcolepsy and sleep disorders, shows promise in treating PSUD, and its therapeutic potential is discussed in this review.
Article
Biochemistry & Molecular Biology
Jana Lubec, Ahmed M. Hussein, Predrag Kalaba, Daniel Daba Feyissa, Edgar Arias-Sandoval, Anita Cybulska-Klosowicz, Mekite Bezu, Tamara Stojanovic, Volker Korz, Jovana Malikovic, Nilima Y. Aher, Martin Zehl, Vladimir Dragacevic, Johann Jakob Leban, Claudia Sagheddu, Judith Wackerlig, Marco Pistis, Merce Correa, Thierry Langer, Ernst Urban, Harald Hoeger, Gert Lubec
Summary: The worldwide increase in cognitive decline calls for the search of pharmacological treatment. Current dopamine transporter (DAT) inhibitors have unwanted side effects due to lack of specificity. A highly specific DAT inhibitor, S-CE-123, was synthesized and tested for its potential to enhance cognitive functions in rats. S-CE-123 showed good bioavailability and improved the performance of aged rats.
Article
Biochemistry & Molecular Biology
Daria S. Kalinina, Vsevolod A. Lyakhovetskii, Oleg V. Gorskii, Polina Yu. Shkorbatova, Natalia V. Pavlova, Elena Yu. Bazhenova, Yurii I. Sysoev, Raul R. Gainetdinov, Pavel E. Musienko
Summary: Dopamine is a critical neurotransmitter involved in controlling muscle tone and body posture. In this study, we investigated the effects of dopamine deficiency on motor capacities and muscle responses to postural disturbance. The results showed that dopamine deficiency led to bradykinesia, rigidity, and postural instability, and affected the initiation pattern of corrective responses. These findings provide insights into the role of dopamine in postural reactions and can be used to study dopamine-related diseases.
Article
Biochemistry & Molecular Biology
Dmitrii S. Traktirov, Ilya R. Nazarov, Valeria S. Artemova, Raul R. Gainetdinov, Nina S. Pestereva, Marina N. Karpenko
Summary: This article explores the roles of dopamine and serotonin in the central nervous system and the impact of knockout of the DAT gene on neurotransmission. The study reveals that excessive dopamine leads to dysregulation of neurotransmission in multiple brain regions and significant effects on the serotonin system. These findings highlight the importance of considering these factors in drug therapies.
Article
Neurosciences
Rosaria Formisano, Katarzyna D. Rosikon, Abhyudai Singh, Harbinder S. Dhillon
Summary: The study examined the mechanisms of dopamine release and clearance, finding that DAT-1 acts as a negative feedback modulator in regulating neurotransmitter vesicle fusion. Through experimental results and a mechanistic model, the dynamics of synaptic vesicle fusion were dissected, and the feedback effects of DAT-1 were compared with dopamine auto-receptors. The findings have broader significance as similar dynamics may be utilized by other synaptic modulators across species.
JOURNAL OF NEUROSCIENCE RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Pawel Grochecki, Irena Smaga, Paulina Surowka, Marta Marszalek-Grabska, Predrag Kalaba, Vladimir Dragacevic, Patrycja Kotlinska, Malgorzata Filip, Gert Lubec, Jolanta H. Kotlinska
Summary: Maternal separation is a major contributor to neurodevelopmental disorders. This study suggests that dopamine signaling plays a key role in maternal separation-induced learning disabilities. The new dopamine transporter inhibitor, CE-123, can effectively counteract the spatial learning and memory deficit caused by maternal separation in rats, particularly in females. It restores cognitive impairment and dopamine signaling in adolescent rats exposed to maternal separation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Adithya Gopinath, Phillip M. Mackie, Leah T. Phan, Rosa Mirabel, Aidan R. Smith, Emily Miller, Stephen Franks, Ohee Syed, Tabish Riaz, Brian K. Law, Nikhil Urs, Habibeh Khoshbouei
Summary: The dopamine transporter (DAT) is not only expressed in the central nervous system and involved in neurological and neuropsychiatric diseases, but also in peripheral immune cells where it regulates immune responses. Blocking DAT activity enhances immune stimulation in macrophages, leading to increased inflammatory response and altered T and B cell populations.
Article
Biology
Inbar Kirshenboim, Ben Aviner, Eyal Itskovits, Alon Zaslaver, Limor Broday
Summary: Underwater divers are at risk of neurological issues due to increased pressure, with this study using the soil nematode Caenorhabditis elegans to investigate dopamine pathway changes under hyperbaric conditions. The findings show that animals respond to pressure changes in a dopamine-dependent biphasic manner, highlighting the role of dopamine signaling in high-pressure responses.
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2021)
Review
Cell Biology
Pepin Marshall
Summary: The application of glial cell line-derived neurotrophic factor (GDNF) has shown positive effects on the survival, development, function, restoration, and protection of dopaminergic neurons in cell cultures and animal models. However, trials using recombinant GDNF protein in late-stage Parkinson's disease patients have had limited success, possibly due to a lack of viable receptor targets in advanced neurodegeneration. Recent research suggests refined approaches to modulating GDNF signaling and using dopamine regulation as a proxy measure for optimal quantity and spatial regulation of GDNF. Basic research on the dopaminergic effects of GDNF in animal models concludes that increasing the number of natively expressing cells can enhance dopamine turnover and maximize neuroprotective and beneficial motor effects while minimizing hyperdopaminergia and side effects. Methodological considerations for measuring dopamine levels and understanding neuroanatomical distinctions will inform future research on this relevant growth factor.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Maria Ptukha, Zoia Fesenko, Anastasia Belskaya, Arina Gromova, Arseniy Pelevin, Natalia Kurzina, Raul R. Gainetdinov, Anna Volnova
Summary: This study evaluated the effect of atomoxetine on the behavior and brain activity of dopamine transporter knockout (DAT-KO) rats, which exhibit ADHD-like behavior. Atomoxetine improved PPI and reduced repetitive behaviors in DAT-KO rats and also influenced the behavior of wild-type rats. Furthermore, it led to significant changes in power spectra and coherence of both DAT-KO and wild type rats.
Article
Pharmacology & Pharmacy
Adithya Gopinath, Tabish Riaz, Emily Miller, Leah Phan, Aidan Smith, Ohee Syed, Stephen Franks, Luis R. Martinez, Habibeh Khoshbouei
Summary: Methamphetamine, a commonly abused psychostimulant, targets the dopamine transporter (DAT) and inhibits dopamine uptake while increasing dopamine release in the brain. It also affects peripheral immune cells expressing DAT, leading to impaired wound healing and increased susceptibility to infection. The study showed that methamphetamine treatment down-regulated DAT expression in innate and adaptive immune cells, without affecting their total numbers. Additionally, serum cytokine distributions were altered in methamphetamine-treated mice. These findings suggest that methamphetamine modulates peripheral immune responses by regulating DAT expression.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Medicine, Research & Experimental
Farina Hanif, Qurat-ul-Ain Amir, Washdev Washdev, Fareena Bilwani, Shabana Usman Simjee, Zeba Haque
Summary: The study did not find an association between the DRD2 rs6275 gene and schizophrenia in the Pakistani population. However, a novel missense SNP at chr11:113412805 was significantly associated with schizophrenia in this population. Further large-scale multicenter studies are needed to confirm this new SNP's association with schizophrenia.
ARCHIVES OF MEDICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Anna Volnova, Natalia Kurzina, Anastasia Belskaya, Arina Gromova, Arseniy Pelevin, Maria Ptukha, Zoia Fesenko, Alla Ignashchenkova, Raul R. Gainetdinov
Summary: Investigating the mechanisms of ADHD and other dopamine-associated conditions is crucial for developing new treatment approaches. This study evaluated the effects of alpha 2A-adrenoceptor agonist guanfacine on behavioral deficits in DAT-KO rats. The results showed that repeated administration of guanfacine improved spatial working memory and behavioral deficits in DAT-KO rats, suggesting the potential use of this drug in balancing dopamine and norepinephrine levels for treatment.
Article
Neurosciences
Charles Sutton, Erin Q. Williams, Hoomam Homsi, Pieter Beerepoot, Reza Nazari, Dong Han, Amy J. Ramsey, Deborah C. Mash, David E. Olson, Bruce Blough, Ali Salahpour
Summary: Mutations in the dopamine transporter gene (SLC6A3) have been linked to Dopamine Transporter Deficiency Syndrome (DTDS), a disease characterized by minimal functional dopamine transporter protein and severe motor symptoms. Two pharmacological chaperones, bupropion and ibogaine, have shown efficacy in rescuing disease-causing variants. In this study, structure-activity relationships (SARs) were explored for these two compounds, identifying the important chemical features required for their chaperone activity. The findings contribute to the development of improved dopamine transporter pharmacological chaperones.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Jun Zhu, Pamela M. Quizon, Yingying Wang, Charles A. Adeniran, Matthew J. Strauss, Ana C. Jimenez-Torres, Palak Patel, Thomas J. Cirino, Shainnel O. Eans, Haylee R. Hammond, Laure S. Deliscar, Priscilla O'Hara, Surendra K. Saini, Edward Ofori, Rakesh H. Vekariya, Sixue Zhang, Omar Moukha-Chafiq, Theresa H. Nguyen, Subramaniam Ananthan, Corinne E. Augelli-Szafran, Chang-Guo Zhan, Jay P. McLaughlin
Summary: This study demonstrates that HIV-1 Tat allosterically modulates dopamine reuptake and interacts with cocaine through the human dopamine transporter. A novel allosteric modulator of DAT, SRI-32743, can attenuate Tat-induced inhibition of dopamine uptake and decrease cocaine-mediated dissociation of [H-3]WIN35,428 binding. This suggests that compounds interacting at DAT allosteric modulatory sites may provide a potential therapeutic intervention for HIV-infected patients with concurrent cocaine abuse.
Article
Psychology, Clinical
Robin Emsley, Stefan du Plessis, Lebogang Phahladira, Hilmar K. Luckhoff, Frederika Scheffler, Sanja Kilian, Retha Smit, Chanelle Buckle, Bonginkosi Chiliza, Laila Asmal
Summary: This study investigated the effects of antipsychotic treatment on brain structural changes in schizophrenia. The results showed plasticity in white matter and basal ganglia associated with antipsychotic treatment, possibly due to the dopamine blocking actions of these drugs. Cortical changes were more closely related to the neurodevelopmental aspects of the illness.
PSYCHOLOGICAL MEDICINE
(2023)
Letter
Medicine, General & Internal
Constanze Kuhlmann, Carla Konstanze Mayer, Mathilda Claassen, Tongai Maponga, Wendy A. Burgers, Roanne Keeton, Catherine Riou, Andrew D. Sutherland, Tasnim Suliman, Megan L. Shaw, Wolfgang Preiser
Letter
Virology
Monray E. Williams, Vurayai Ruhanya, Robert H. Paul, Jonathan C. Ipser, Dan J. Stein, John A. Joska, Petrus J. W. Naude
JOURNAL OF MEDICAL VIROLOGY
(2022)
Article
Neurosciences
Chanelle Juanita Hendrikse, Stefan Plessis, Hilmar Klaus Luckhoff, Matthijs Vink, Leigh Luella Heuvel, Freda Scheffler, Lebogang Phahladira, Retha Smit, Laila Asmal, Soraya Seedat, Robin Emsley
Summary: This study found a significant effect of childhood abuse on ventral striatum activation during reward anticipation in healthy adults, while there were no effects on orbitofrontal cortex activation during reward outcome.
JOURNAL OF NEUROSCIENCE RESEARCH
(2022)
Article
Neurosciences
Jonathan C. Ipser, John Joska, Tatum Sevenoaks, Hetta Gouse, Carla Freeman, Tobias Kaufmann, Ole A. Andreassen, Steve Shoptaw, Dan J. Stein
Summary: The study found that heavy drinkers (with or without HIV) have greater brain aging. The cingulate and parietal cortex, as well as subcortical brain regions, are associated with age differences. Higher drinking scores are correlated with larger age differences, while CD4 count or HIV viral load is not related.
JOURNAL OF NEUROVIROLOGY
(2022)
Article
Neurosciences
Vurayai Ruhanya, Graeme Brendon Jacobs, Robert H. Paul, John A. Joska, Soraya Seedat, George Nyandoro, Richard H. Glashoff, Susan Engelbrecht
Summary: The study shows that genetic variation and selection pressure on the Tat gene are associated with neurocognitive impairment in HIV-infected individuals, indicating the importance of specific amino acid residues and codons in the development and severity of the disease.
JOURNAL OF NEUROVIROLOGY
(2022)
Article
Psychiatry
Lebogang Phahladira, Laila Asmal, Hilmar K. Luckhoff, Stefan du Plessis, Freda Scheffler, Retha Smit, Bonginkosi Chiliza, Robin Emsley
Summary: This study replicated the two-factor structure for PANSS negative symptom subdomains in schizophrenia and found that they are closely related and respond similarly to antipsychotic treatment. The experiential subdomain is affected by depression, while the expressive subdomain is affected by extrapyramidal symptoms.
SCHIZOPHRENIA RESEARCH
(2022)
Article
Psychiatry
Hilmar Klaus Luckhoff, Laila Asmal, Frederika Scheffler, Stefan du Plessis, Bonginkosi Chiliza, Retha Smit, Lebogang Phahladira, Robin Emsley
Summary: This study examined the associations of biological sex and gender role endorsement with indicators of neurodevelopmental compromise in patients with schizophrenia. The findings showed that lower masculinity scores were significantly correlated with poorer premorbid adjustment, sensory integration deficits, and worse overall cognitive performance. Gender, on the other hand, showed different associations with indicators of neurodevelopmental compromise compared to biological sex.
SCHIZOPHRENIA RESEARCH
(2022)
Article
Psychology, Clinical
Eamonn Kennedy, Emily L. Dennis, Hannah M. Lindsey, Terri deRoon-Cassini, Stefan Du Plessis, Negar Fani, Milissa L. Kaufman, Nastassja Koen, Christine L. Larson, Sarah Laskowitz, Lauren A. M. Lebois, Rajendra A. Morey, Mary R. Newsome, Cori Palermo, Nicholas J. Pastorek, Abigail Powers, Randall Scheibel, Soraya Seedat, Antonia Seligowski, Dan J. Stein, Jennifer Stevens, Delin Sun, Paul Thompson, Maya Troyanskaya, Sanne J. H. van Rooij, Amanda A. Watts, Carissa W. Tomas, Wright Williams, Frank G. Hillary, Mary Jo Pugh, Elisabeth A. Wilde, David F. Tate
Summary: This study uses a multisite mega analysis to derive quantitative recommendations for equating scores across measures of PTSD severity. The results suggest that harmonization and covariate adjustments can significantly improve inference of scores across different instruments.
Review
Health Policy & Services
Adele Munsami, Anna J. Dreyer, Goodman Sibeko, Hetta Gouse, Sam Nightingale, John A. Joska
Summary: Mental health and neurocognitive functioning are important concerns for people living with HIV, but healthcare workers in Africa lack knowledge about the relationship between HIV and NCI. There is a gap in training interventions addressing NCI in Africa, and further research is needed to develop and evaluate training interventions for healthcare workers delivering HIV services in this setting.
AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV
(2023)
Article
Public, Environmental & Occupational Health
Jasper S. Lee, Sierra A. Bainter, Alexander C. Tsai, Lena S. Andersen, Amelia M. Stanton, Jessica F. Magidson, Ashraf Kagee, John A. Joska, Conall O'Cleirigh, Steven A. Safren
Summary: This study surveyed people with HIV in South Africa and explored the interrelationships between syndemic problems. The findings showed that syndemic problems, such as depression, substance use, and food insecurity, were common among people with HIV in South Africa. Network analysis identified several significant associations and clusters of syndemic problems. These findings have important implications for improving HIV treatment outcomes in sub-Saharan Africa.
Article
Immunology
Patrick G. A. Oomen, Charlotte S. S. Hakkers, Joop E. E. Arends, Guido E. L. van der Berk, Pascal Pas, Andy I. M. Hoepelman, Berend J. J. van Welzen, Stefan du Plessis
Summary: This study aimed to investigate the effect of the antiretroviral drug efavirenz (EFV) on reward processing. The results showed that EFV did not have a significant impact on reward anticipation and reward outcome. This suggests that EFV may not affect motivational control.
AIDS RESEARCH AND HUMAN RETROVIRUSES
(2023)
Article
Biochemistry & Molecular Biology
Constantinos Constantinides, Laura K. M. Han, Clara Alloza, Linda Antonella Antonucci, Celso Arango, Rosa Ayesa-Arriola, Nerisa Banaj, Alessandro Bertolino, Stefan Borgwardt, Jason Bruggemann, Juan Bustillo, Oleg Bykhovski, Vince Calhoun, Vaughan Carr, Stanley Catts, Young-Chul Chung, Benedicto Crespo-Facorro, Covadonga M. Diaz-Caneja, Gary Donohoe, Stefan Du Plessis, Jesse Edmond, Stefan Ehrlich, Robin Emsley, Lisa T. Eyler, Paola Fuentes-Claramonte, Foivos Georgiadis, Melissa Green, Amalia Guerrero-Pedraza, Minji Ha, Tim Hahn, Frans A. Henskens, Laurena Holleran, Stephanie Homan, Philipp Homan, Neda Jahanshad, Joost Janssen, Ellen Ji, Stefan Kaiser, Vasily Kaleda, Minah Kim, Woo-Sung Kim, Matthias Kirschner, Peter Kochunov, Yoo Bin Kwak, Jun Soo Kwon, Irina Lebedeva, Jingyu Liu, Patricia Mitchie, Stijn Michielse, David Mothersill, Bryan Mowry, Victor Ortiz-Garcia de la Foz, Christos Pantelis, Giulio Pergola, Fabrizio Piras, Edith Pomarol-Clotet, Adrian Preda, Yann Quide, Paul E. Rasser, Kelly Rootes-Murdy, Raymond Salvador, Marina Sangiuliano, Salvador Sarro, Ulrich Schall, Andre Schmidt, Rodney J. Scott, Pierluigi Selvaggi, Kang Sim, Antonin Skoch, Gianfranco Spalletta, Filip Spaniel, Sophia Thomopoulos, David Tomecek, Alexander S. Tomyshev, Diana Tordesillas-Gutierrez, Therese van Amelsvoort, Javier Vazquez-Bourgon, Daniela Vecchio, Aristotle Voineskos, Cynthia S. Weickert, Thomas Weickert, Paul M. Thompson, Lianne Schmaal, Theo G. M. van Erp, Jessica Turner, James H. Cole, Danai Dima, Esther Walton
Summary: Schizophrenia patients show evidence of advanced brain ageing, which is not associated with clinical characteristics.
MOLECULAR PSYCHIATRY
(2023)
Article
Psychiatry
Stefan du Plessis, Ganesh B. Chand, Guray Erus, Lebogang Phahladira, Hilmar K. Luckhoff, Retha Smit, Laila Asmal, Daniel H. Wolf, Christos Davatzikos, Robin Emsley
Summary: This study identified two neuroanatomical signatures derived from machine learning that are associated with the neurodevelopmental and treatment-responsive components of schizophrenia. Signature 1 is associated with widespread grey matter volume reductions, while Signature 2 is associated with larger basal ganglia and internal capsule volumes. Patients had higher expression of Signature 1 compared to controls, while Signature 2 expression significantly increased with treatment.
SCHIZOPHRENIA BULLETIN
(2023)
Review
Psychology, Clinical
Alberta S. J. Van der Watt, Annerine Roos, Stefan Du Plessis, Eric Bui, Elmien Lesch, Soraya Seedat
Summary: Non-marital romantic relationship breakups among university students can lead to severe psychological distress and potential trauma, with a strong association to completed suicide. Utilizing attachment theory and neuroscience to examine the impact of these breakups on brain activity is justified and may lead to new treatments for posttraumatic stress disorder.
JOURNAL OF COUPLE & RELATIONSHIP THERAPY-INNOVATIONS IN CLINICAL AND EDUCATIONAL INTERVENTIONS
(2022)