Review
Biochemistry & Molecular Biology
Adriana Della Pietra, Juha Savinainen, Rashid Giniatullin
Summary: This thematic review discusses the potential use of inhibiting endocannabinoid-degrading enzymes to increase endocannabinoid levels and alleviate migraine pain. It also explores the migraine pain signaling pathways, the complex effects of endocannabinoids in pain modulation, and emerging inhibitors to target these pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Justin Matheson, Xin Ming Matthew Zhou, Zoe Bourgault, Bernard Le Foll
Summary: Research suggests that modulating enzymes involved in the synthesis and degradation of endocannabinoids, such as FAAH, MAGL, and DAGL, may be an effective strategy for treating obesity. In animal models, inhibiting FAAH tends to promote obesity, while genetic deletion of Mgll and Dagla, as well as pharmacological inhibition of DAGL, tends to reduce body weight and improve metabolic state. The effects of Mgll manipulation, however, are tissue-dependent and require further investigation.
Article
Biochemical Research Methods
Reshed Abohalaka, Turgut Emrah Bozkurt, Tuba Recber, Sevgen Celik Onder, Emirhan Nemutlu, Sedef Kir, Inci Sahin-Erdemli
Summary: The endocannabinoid system plays a crucial role in respiratory diseases, and modulation of endocannabinoid levels can prevent airway inflammation and hyperreactivity. Treatment with FAAH or MAGL inhibitors locally or systemically did not cause significant histopathological changes in mice, but had a significant impact on the levels of endocannabinoid metabolites in the lungs.
BIOMEDICAL CHROMATOGRAPHY
(2022)
Article
Biochemistry & Molecular Biology
Marek Toczek, Piotr Ryszkiewicz, Patryk Remiszewski, Eberhard Schlicker, Anna Krzyzewska, Hanna Kozlowska, Barbara Malinowska
Summary: Enhancement of endocannabinoid tone may benefit hypertension. JZL195, a dual inhibitor of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), exhibited weak hypotensive and bradycardic effects in spontaneously hypertensive rats (SHR) but not in normotensive Wistar Kyoto rats (WKY). Chronic administration of JZL195 effectively prevented the progression of hypertension without tolerance, while also slightly reducing heart rate in WKY and preventing weight gain in both groups.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Neurosciences
Karen Jaqueline Paredes-Ruiz, Karla Chavira-Ramos, Mario Orozco-Morales, Cimen Karasu, Alexey A. Tinkov, Michael Aschner, Abel Santamaria, Ana Laura Colin-Gonzalez
Summary: The endocannabinoid system is a complex physiological system composed of endogenous cannabinoids, components involved in their synthesis and degradation, as well as a variety of cannabinoid receptors. Dysregulation of this system has been linked to pathological conditions, highlighting the potential therapeutic value of enhancing endocannabinoid levels and regulating their metabolism. Inhibitors of degradation/reuptake have been suggested as important strategies for modulating the endocannabinoid system, potentially offering new avenues for treating various disorders.
NEUROTOXICITY RESEARCH
(2021)
Article
Chemistry, Medicinal
Alan Fulp, Sarah Bingham, Bethany Fisler, Felice Kho, Joshua Kim, So Jung Kim, Tabitha Martin, Bailey Mims, Kezia Reji Thomas, Grace Roe, Julia Spiotta, Julianna Young, Matthew Lazenka
Summary: A small library of FAAH and dual FAAH/MAGL inhibitors designed for peripheral selectivity were studied. Three compounds with desirable FAAH inhibition and reduced permeability were identified. Further assays confirmed that one compound was a relative selective FAAH inhibitor, while the other one exhibited characteristics of a true dual enzyme inhibitor.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Neurosciences
Hiroki Kawashima, Yuri Aono, Yuriko Watanabe, John L. Waddington, Tadashi Saigusa
Summary: This study demonstrates that accumbal OX2 receptors, not OX1 receptors, inhibit basal dopamine efflux, while blocking OX2 receptors increases dopamine efflux. OX1 receptors have no effect on dopamine efflux.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2022)
Article
Medicine, General & Internal
Saki Sultana, Geraint Berger, Christian Lehmann
Summary: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition with unknown etiology and limited treatment options. Modulating the endogenous cannabinoid system (ECS) has shown benefits in alleviating pain and inflammation associated with IC/BPS.
Review
Psychiatry
Ardavan Mohammad Aghaei, Alexandra Saali, Maria Alejandra Canas, Jeremy Weleff, Deepak Cyril D'Souza, Gustavo A. Angarita, Anahita Bassir Nia
Summary: This paper reviews the clinical and preclinical literature on the dysregulation of the endocannabinoid system (ECS) after exposure to opioids. The results show that opioids disrupt various ECS components in specific brain regions. However, the literature results are heterogeneous and contradictory, suggesting the need for further research to determine the effects of opioids on ECS components in different brain regions.
PSYCHIATRY RESEARCH
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Keisuke Takahata, Chie Seki, Yasuyuki Kimura, Manabu Kubota, Masanori Ichise, Yasunori Sano, Yasuharu Yamamoto, Kenji Tagai, Hitoshi Shimada, Soichiro Kitamura, Kiwamu Matsuoka, Hironobu Endo, Hitoshi Shinotoh, Kazunori Kawamura, Ming-Rong Zhang, Yuhei Takado, Makoto Higuchi
Summary: This study demonstrates the first visualization of MAGL in the human brain using the novel PET ligand F-18-T-401. The results confirm the reliability of F-18-T-401-PET for quantification and stability analysis of MAGL in vivo.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2022)
Article
Chemistry, Medicinal
Francesca Intranuovo, Leonardo Brunetti, Pietro DelRe, Giuseppe Felice Mangiatordi, Angela Stefanachi, Antonio Laghezza, Mauro Niso, Francesco Leonetti, Fulvio Loiodice, Alessia Ligresti, Magdalena Kostrzewa, Jose Brea, Maria Isabel Loza, Eddy Sotelo, Michele Saviano, Nicola Antonio Colabufo, Chiara Riganti, Carmen Abate, Marialessandra Contino
Summary: CB2R, a receptor in the endocannabinoid system, is overexpressed in inflammatory pathologies and its activation has anti-inflammatory effects. FAAH is an enzyme responsible for breaking down endocannabinoids, and inhibiting FAAH while activating CB2R may have synergistic anti-inflammatory effects. Through chemical analysis, a small library of adamantyl-benzamides was designed as potential dual agents to activate CB2R and inhibit FAAH. The new compounds showed promising anti-inflammatory effects by reducing pro-inflammatory cytokines and increasing anti-inflammatory cytokines.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Francesca Seghetti, Silvia Gobbi, Federica Belluti, Angela Rampa, Alessandra Bisi
Summary: Polypharmacology offers potential for improving the treatment of neurodegenerative diseases, with a focus on the endocannabinoid system and the cannabinoid receptor subtype 2 as promising therapeutic targets. Indirect modulation of this system through the inhibition of key enzymes responsible for endocannabinoids metabolism may significantly impact neurodegenerative processes.
CURRENT MEDICINAL CHEMISTRY
(2022)
Review
Neurosciences
Faith Borgan, Michelle Kokkinou, Oliver Howes
Summary: Research on the CB1 receptor in schizophrenia has shown a reduction in animal models and clinical studies, but inconsistent results have been reported in ex vivo studies. The authors discuss methodological reasons for these discrepancies and explore how CB1 receptor dysfunction may contribute to the pathophysiology of schizophrenia, as well as the potential for the receptor to be a therapeutic target.
BIOLOGICAL PSYCHIATRY-COGNITIVE NEUROSCIENCE AND NEUROIMAGING
(2021)
Article
Biochemistry & Molecular Biology
Jaisan Islam, K. C. Elina, Soochong Kim, Hyong Kyu Kim, Young Seok Park
Summary: The study found that optogenetic stimulation of NAcc GABAergic neurons in TN animal model could reduce neuronal activity and significantly improve behavioral responses. Microdialysis analysis also revealed significant alterations in neurotransmitter levels in NAcc upon optic stimulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Klara Danielsson, Oona Lagstrom, Mia Ericson, Bo Soderpalm, Louise Adermark
Summary: The study suggests that repeated amphetamine exposure leads to selective effects on dopamine signaling in striatal subregions, explaining why tolerance develops towards the drug's rewarding effects but not its psychosis inducing properties.
Correction
Multidisciplinary Sciences
Joshua Obermayer, Antonio Luchicchi, Tim S. Heistek, Sybren F. de Kloet, Huub Terra, Bastiaan Bruinsma, Ouissame Mnie-Filali, Christian Kortleven, Anna A. Galakhova, Ayoub J. Khalil, Tim Kroon, Allert J. Jonker, Roel de Haan, Wilma D. J. van de Berg, Natalia A. Goriounova, Christiaan P. J. de Kock, Tommy Pattij, Huibert D. Mansvelder
NATURE COMMUNICATIONS
(2020)
Article
Medicine, Research & Experimental
Jasper A. Heinsbroek, Taco J. De Vries, Jamie Peters
Summary: This review discusses the mechanisms by which glutamate, dopamine, and opioid signaling interact to mediate the primary rewarding effects of opioids, and covers the glutamatergic systems and circuits that mediate the expression, extinction, and reinstatement of opioid seeking over the course of opioid addiction.
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
(2021)
Article
Multidisciplinary Sciences
Esther Visser, Mariana R. Matos, Rolinka J. van der Loo, Nathan J. Marchant, Taco J. de Vries, August B. Smit, Michel C. van den Oever
Article
Substance Abuse
Tommy Pattij, Yvar van Mourik, Leontien Diergaarde, Taco J. de Vries
DRUG AND ALCOHOL DEPENDENCE
(2020)
Article
Biochemistry & Molecular Biology
Huub Terra, Bastiaan Bruinsma, Sybren F. de Kloet, Marcel van der Roest, Tommy Pattij, Huibert D. Mansvelder
Review
Behavioral Sciences
Maria Nalberczak Skora, Tommy Pattij, Anna Beroun, Georgios Kogias, Dirk Mielenz, Taco de Vries, Kasia Radwanska, Christian P. Mueller
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2020)
Article
Biochemical Research Methods
Antonio Luchicchi, Tommy Pattij, John Noel M. Viana, Sybren de Kloet, Nathan Marchant
Summary: There has been significant progress in understanding brain function over the last century, with the use of viral vectors playing a crucial role in the development of techniques like optogenetics and chemogenetics. The introduction of adeno-associated virus and the retrograde tracer canine-associated-2 Cre virus have been pivotal in achieving optimal visualization and interrogation of chemically-specific neuronal populations and projections.
JOURNAL OF NEUROSCIENCE METHODS
(2021)
Review
Nutrition & Dietetics
Janette de Goede, Kerstin G. van der Mark-Reeuwijk, Kees P. Braun, Saskia le Cessie, Sarah Durston, Rutger C. M. E. Engels, Anna E. Goudriaan, Karel G. M. Moons, Wilma A. M. Vollebergh, Taco J. de Vries, Reinout W. Wiers, Jaap Oosterlaan
Summary: Alcohol consumption in young people may negatively affect brain function and development, including abnormal gray matter development and increased risk of alcohol use disorder. Current evidence on white matter, brain activity, cognitive function, and educational achievement remains limited or unclear.
ADVANCES IN NUTRITION
(2021)
Article
Multidisciplinary Sciences
Sybren F. de Kloet, Bastiaan Bruinsma, Huub Terra, Tim S. Heistek, Emma M. J. Passchier, Alexandra R. van den Berg, Antonio Luchicchi, Rogier Min, Tommy Pattij, Huibert D. Mansvelder
Summary: The study identifies four distinct populations of prefrontal neurons projecting to different sub-regions of the striatum and thalamus, each playing a discrete role in the regulation of cognitive control. Dorsal and ventral mPFC circuits exhibit differential synaptic inputs to postsynaptic striatal and thalamic neurons, potentially amplifying distinct pathways underlying cognitive control. Chemogenetic silencing of specific mPFC projections to thalamic subregions oppositely regulate cognitive control, highlighting the complex mechanisms involved in behavior regulation.
NATURE COMMUNICATIONS
(2021)
Article
Neuroimaging
Antonia Kaiser, Liesbeth Reneman, Paul J. Lucassen, Taco J. de Vries, Anouk Schrantee, Anne Marije Kaag
Summary: The study examined the neural mechanisms underlying the interaction between working memory (WM) and emotional reactivity (ER) in adult ADHD participants, finding that taxing WM reduced reactivity to emotional stimuli in heavy drinkers but did not affect neural correlates of ER in ADHD participants. No impairments in WM or ER were found in the ADHD group, possibly due to the relatively unimpaired ADHD population and well-matched control group. Further investigation is needed to determine if targeting WM may be effective in participants with severe ER impairments in ADHD.
BRAIN IMAGING AND BEHAVIOR
(2022)
Article
Neurosciences
Elham Alaee, Parisa Moazen, Tommy Pattij, Saeed Semnanian, Hossein Azizi
Summary: Prenatal exposure to morphine has lasting effects on cognitive abilities and inhibitory control in offspring, leading to deficits in task learning and attention in adult life.
PSYCHOPHARMACOLOGY
(2021)
Article
Neurosciences
Maryam Azadi, Parisa Moazen, Joost Wiskerke, Saeed Semnanian, Hossein Azizi
Summary: Paternal opiate exposure during adolescence primarily impairs inhibitory control in male progeny, as evidenced by delayed learning under high cognitive load and decreased ability to exert inhibitory control under drug-free baseline conditions.
PSYCHOPHARMACOLOGY
(2021)
Review
Behavioral Sciences
Marianne Amalric, Tommy Pattij, Ioannis Sotiropoulos, Joana M. Silva, Nuno Sousa, Samira Ztaou, Cristiano Chiamulera, Lars U. Wahlberg, Dwaine F. Emerich, Giovanna Paolone
Summary: Historically, studies on neurodegenerative diseases have largely examined alterations in specific neuronal populations, but it is becoming increasingly clear that the integrity of multiple interconnected neuronal circuits regulates various brain activities in mammals. The dopaminergic and cholinergic systems play crucial roles in orchestrating cognitive and non-cognitive symptoms in PD and AD.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2021)
Article
Biology
Hussein Ghareh, Isis Alonso-Lozares, Dustin Schetters, Rae J. Herman, Tim S. Heistek, Yvar Van Mourik, Philip Jean-Richard-dit-Bressel, Gerald Zernig, Huibert D. Mansvelder, Taco J. De Vries, Nathan J. Marchant
Summary: This study shows the critical role of environmental contexts in promoting nicotine relapse and the importance of aIC activity in context-induced relapse.
Article
Neurosciences
Ruey-Ming Liao, Tommy Pattij
Summary: This article reviews early and recent experiments using brain lesions and drug infusions to investigate the neural substrates and neuropharmacological basis of differential reinforcement of low-rate response (DRL) behavior. The findings suggest that certain cortical and subcortical areas are involved in DRL behavior and disruption of dopamine or serotonin neurotransmission can alter this behavior.
BRAIN RESEARCH BULLETIN
(2022)