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
Radiology, Nuclear Medicine & Medical Imaging
Igor D. Grachev, Philipp M. Meyer, Georg A. Becker, Marcus Bronzel, Doug Marsteller, Gina Pastino, Ole Voges, Laura Rabinovich, Helena Knebel, Franziska Zientek, Michael Rullmann, Bernhard Sattler, Marianne Patt, Thilo Gerhards, Maria Strauss, Andreas Kluge, Peter Brust, Juha-Matti Savola, Mark F. Gordon, Michal Geva, Swen Hesse, Henryk Barthel, Michael R. Hayden, Osama Sabri
Summary: Pridopidine demonstrates high affinity for the S1R in clinical trials, with near complete occupancy at a clinically relevant single dose of 90 mg. Minimal occupancy is seen at the D2/D3R, indicating pridopidine's selectivity as an S1R ligand. The dose-S1R occupancy relationship suggests cooperative binding of pridopidine to the S1R.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(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
Pharmacology & Pharmacy
Simeone Marino, Hassan Jassar, Dajung J. J. Kim, Manyoel Lim, Thiago D. D. Nascimento, Ivo D. D. Dinov, Robert A. A. Koeppe, Alexandre F. F. DaSilva
Summary: This study utilized a novel machine learning method to accurately identify migraine patients based on the analysis of central mu-opioid and dopamine D2/D3 receptors. The results showed that dysfunction in the μ-opioid and D2/D3 receptors in the neurotransmission of migraine patients may partly explain the severe impact of migraine and associated neuropsychiatric comorbidities.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Neurosciences
Joseph B. Mandeville, Jonah Weigand-Whittier, Hsiao-Ying Wey
Summary: In this study, the researchers compared the receptor occupancy induced by amphetamine (AMP) in wild-type (WT) and internalization-compromised beta-arrestin-2 knockout (KO) mice. They found that at 3 hours after AMP treatment, WT mice showed significantly lower binding potential compared to KO mice, indicating that receptor internalization can greatly reduce occupancy on the second challenge.
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)
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, Multidisciplinary
Yonghao Mi, Enliang Wang, Zack Dube, Tian Wang, A. Y. Naumov, D. M. Villeneuve, P. B. Corkum, Andre Staudte
Summary: Using near-infrared, femtosecond laser pulses and coincidence momentum imaging, it is found that the dominant channel after photoionization of a deuterium molecular dimer (D-2-D-2) is the ejection of a deuterium atom within a few hundred femtoseconds, leading to the formation of D-3(+). This pathway of D-3(+) formation from ultracold D-2-D-2 gas may provide insights into the high abundance of H-3(+) in the interstellar medium.
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
Multidisciplinary Sciences
Nace Mikus, Christoph Eisenegger, Christoph Mathys, Luke Clark, Ulrich Mueller, Trevor W. Robbins, Claus Lamm, Michael Naef
Summary: The study investigates the impact of the D2/D3 dopamine receptor antagonist sulpiride on learning about other people's prosocial attitudes. The results show that sulpiride increases the volatility of beliefs, leading to higher precision weights on prediction errors. This effect is more significant in participants with genetically conferred higher dopamine availability and remains even after controlling for working memory performance. The findings demonstrate the importance of D2 receptors in regulating belief updating in a social context.
NATURE COMMUNICATIONS
(2023)
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
Yasuharu Yamamoto, Keisuke Takahata, Manabu Kubota, Harumasa Takano, Hiroyoshi Takeuchi, Yasuyuki Kimura, Yasunori Sano, Shin Kurose, Hiroshi Ito, Masaru Mimura, Makoto Higuchi
Summary: The study revealed a significant positive correlation between DA synthesis capacity and DA transporter availability in the putamen, but no significant correlation between DA synthesis capacity and D2 receptor availability in the striatum, indicating a relationship between DA synthesis capacity and reuptake, while the total abundance of D2 receptors may not directly participate in the regulatory mechanism.
Review
Biochemistry & Molecular Biology
Kavya Prasad, Erik F. J. de Vries, Philip H. Elsinga, Rudi A. J. O. Dierckx, Aren van Waarde
Summary: Adenosine and dopamine interact antagonistically in living mammals via adenosine A(2A) and dopamine D-2 receptors. These interactions mainly occur in striatal neurons and astrocytes, and may have therapeutic potential for Parkinson's disease, schizophrenia, substance abuse, and attention deficit-hyperactivity disorder.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Psychiatry
Gabriel Bastien, Christina McAnulty, Omar Ledjiar, M. Eugenia Socias, Bernard Le Foll, Ron Lim, Ahmed N. Hassan, Suzanne Brissette, Stephanie Marsan, Annie Talbot, Didier Jutras-Aswad
Summary: This study aimed to evaluate the effectiveness of flexible take-home dosing of buprenorphine/naloxone (BUP/NX) and methadone standard model of care in reducing depressive symptoms in people with prescription-type opioid use disorder (POUD). The results showed that both BUP/NX and methadone had similar effectiveness in decreasing comorbid depressive symptoms in people with POUD.
CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE
(2023)
Article
Psychiatry
Sarah E. Watling, Samantha Jagasar, Tina McCluskey, Jerry Warsh, Shawn G. Rhind, Peter Truong, Sofia Chavez, Sylvain Houle, Junchao Tong, Stephen J. Kish, Isabelle Boileau
Summary: Preliminary data suggests that chronic methamphetamine (MA) use may cause oxidative stress and inflammation in the brain. This study aimed to investigate the levels of the antioxidant glutathione (GSH) in the brains of chronic MA users and explore the relationship between peripheral immunoinflammatory biomarkers and brain GSH concentrations. The results showed that GSH levels did not differ between MA users and healthy controls, but several immunoinflammatory biomarkers were significantly elevated in MA users and correlated with brain GSH levels.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Sonja Elsaid, Peter Truong, Napapon Sailasuta, Bernard Le Foll
Summary: This study evaluated the back-to-back and day-to-day reproducibility of GABA+ in healthy volunteers using a 3 Tesla MRI scanner and the MEGA-PRESS technique. The results showed excellent repeatability and reliability of GABA+ in the dmPFC/ACC and dlPFC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Health Care Sciences & Services
Soyeon Kim, Natalie Rajack, Shawn E. Mondoux, Vitor S. Tardelli, Nathan J. Kolla, Bernard Le Foll
Summary: COVID-19 pandemic has led to a mental health crisis and increased substance use worldwide. This study aims to examine the trends and characteristics of substance use-related emergency department visits among adolescents and young adults in Ontario, Canada during the pandemic.
JOURNAL OF EVALUATION IN CLINICAL PRACTICE
(2023)
Editorial Material
Neurosciences
Kelly Smart, Isabelle Boileau
JOURNAL OF PSYCHIATRY & NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Sarah E. E. Watling, Talwinder Gill, Erin V. V. Gaudette, J. Don Richardson, Tina McCluskey, Junchao Tong, Jeffrey H. H. Meyer, Jerry Warsh, Rakesh Jetly, Michael G. G. Hutchison, Shawn G. G. Rhind, Sylvain Houle, Stephen J. J. Kish, Isabelle Boileau
Summary: This study examined the activation of microglia in individuals with occupation-related PTSD and its relationship with cortisol levels. The results showed non-significant elevation of microglia activation in fronto-limbic brain regions of PTSD participants. However, significantly higher microglia activation was observed in those with frequent cannabis use. The findings suggest a potential link between microglial activation, cannabis use, and the dysregulation of the hypothalamic-pituitary-adrenal-axis.
SCIENTIFIC REPORTS
(2023)
Article
Psychiatry
Joeffre Braga, Mariel Lepra, Stephen J. Kish, Pablo. M. Rusjan, Zahra Nasser, Natasha Verhoeff, Neil Vasdev, Michael Bagby, Isabelle Boileau, M. Ishrat Husain, Nathan Kolla, Armando Garcia, Thomas Chao, Romina Mizrahi, Khunsa Faiz, Erica L. Vieira, Jeffrey H. Meyer
Summary: This study investigated the levels of gliosis marker TSPO V-T in the brain of COVID-DC patients. The study found that COVID-DC patients had higher levels of TSPO V-T compared to healthy controls, especially in the ventral striatum and dorsal putamen. This finding may explain the persistent depressive and cognitive symptoms in COVID-DC patients.
Article
Psychiatry
Sarah E. Watling, Shawn G. Rhind, Jerry Warsh, Duncan Green, Tina McCluskey, Junchao Tong, Peter Truong, Sofia Chavez, J. Don Richardson, Stephen J. Kish, Isabelle Boileau
Summary: This study investigated the concentrations of glutathione (GSH) in the brain and blood markers in individuals with posttraumatic stress disorder (PTSD) compared to healthy controls (HC). The results showed no significant differences in GSH concentrations between PTSD and HC, but potential differences were found in peripheral blood markers. Future research should explore these relationships in larger samples.
FRONTIERS IN PSYCHIATRY
(2023)
Review
Health Care Sciences & Services
Leen Magarbeh, Ilona Gorbovskaya, Richard Wells, Reuven Jhirad, Bernard Le Foll, Daniel J. Mueller
Summary: There has been an increase in accidental opioid-overdose deaths worldwide. This review focuses on the use of pharmacogenetics to predict causes of accidental opioid-overdose death, supported by a literature search and pilot study. The review includes 18 studies that demonstrate the potential of genetic testing, particularly CYP2D6, CYP2B6, and CYP3A4/5 genotyping, in identifying abnormal opioid and metabolite blood concentrations. The pilot study shows an enrichment of the CYP2B6*4 allele in methadone-overdose cases compared to the general population. These findings emphasize the importance of pharmacogenetics in determining vulnerability to opioid overdose.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Neurosciences
Nadia Boachie, Erin Gaudette, Richard P. Bazinet, Lin Lin, Rachel F. Tyndale, Esmaeil Mansouri, Marilyn A. Huestis, Junchao Tong, Bernard Le Foll, Stephen J. Kish, Tony P. George, Isabelle Boileau
Summary: Our preliminary findings suggest that the activity of the endocannabinoid system is elevated in chronic cannabis users. Further studies are needed to examine endocannabinoids and NAEs during prolonged abstinence and the potential role of DHEA in craving.
Review
Psychology, Clinical
Benedikt Fischer, Wayne Hall, Thiago M. Fidalgo, Eva Hoch, Bernard Le Foll, Maria-Elena Medina-Mora, Jens Reimer, Philip G. Tibbo, Didier Jutras-Aswad
Summary: This study reviewed the risk factors related to cannabis use and psychosis outcomes, providing recommendations for risk reduction. Genetic risks, mental health/substance use problem histories, early age-of-use-onset, frequency-of-use, product composition, use mode, and other substance co-use all influence psychosis risks. Reducing these risk factors can decrease the occurrence of adverse psychosis outcomes.
JOURNAL OF DUAL DIAGNOSIS
(2023)
Article
Pharmacology & Pharmacy
Patricia Di Ciano, Bruna Brands, Andrew Fares, Madison Wright, Gina Stoduto, Patrick Byrne, Michael McGrath, Omer S. M. Hasan, Bernard Le Foll, Christine M. Wickens
Summary: This study investigates the relationship between Delta 9-Tetrahydrocannabinol (THC) levels in blood, urine, and saliva and driving impairment, measured by weaving in a driving simulator. The results show that there is no clear linear relationship between blood THC concentration and weaving. However, when blood THC levels exceed the legal limit, driving impairment is significantly increased. Specified thresholds for THC in blood and saliva may be able to detect driving impairment.
CANNABIS AND CANNABINOID RESEARCH
(2023)
Article
Substance Abuse
Helena Zhang, Emily Gilbert, Sarwar Hussain, Scott Veldhuizen, Bernard Le Foll, Peter Selby, Laurie Zawertailo
Summary: This study aims to evaluate whether the presence of depressive symptoms affects the effectiveness of bupropion and varenicline in smoking cessation. The results show that individuals with depressive symptoms at baseline are less likely to quit smoking successfully. Therefore, it is important to assess patients for depressive symptoms when planning to quit smoking in order to determine the appropriate treatment approach.
NICOTINE & TOBACCO RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Intishar Kazi, Meghan J. Chenoweth, Didier Jutras-Aswad, Keith Ahamad, M. Eugenia Socias, Bernard Le Foll, Rachel F. Tyndale
Summary: Methadone and buprenorphine/naloxone are effective treatments for opioid use disorder, but individual responses can vary due to genetic factors. A study investigated the association between genetic variants and clinical outcomes in patients receiving these treatments for 24 weeks. The results showed that OPRM1 gene rs1799971 variant was associated with a better response to methadone treatment, with individuals carrying the AA genotype having more opioid-free urine screens.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Psychology, Clinical
Laurent Elkrief, Gabriel Bastien, Christina McAnulty, Hamzah Bakouni, Francois-Olivier Hebert, M. Eugenia Socias, Bernard Le Foll, Ron Lim, Omar Ledjiar, Stephanie Marsan, Suzanne Brissette, Didier Jutras-Aswad
Summary: This study examined the effects of recent cannabis use on opioid use, craving, and withdrawal symptoms in individuals participating in a randomized controlled trial. The results showed that cannabis use was not significantly associated with these outcomes.
JOURNAL OF SUBSTANCE USE & ADDICTION TREATMENT
(2023)