Article
Neurosciences
A. G. Sartim, J. Marques, K. M. Silveira, P. H. Gobira, F. S. Guimaraes, G. Wegener, S. R. Joca
Summary: The study found that CBD can exhibit antidepressant effects without causing hyperactivity, and it can also inhibit the psychostimulant effects induced by ketamine. The combined administration of CBD and ketamine may be a promising therapeutic strategy for achieving antidepressant effects while reducing unwanted side effects.
Article
Neurosciences
Panos Zanos, Kyle A. Brown, Polymnia Georgiou, Peixiong Yuan, Carlos A. Zarate Jr, Scott M. Thompson, Todd D. Gould
Summary: Ketamine, a well-known NMDA receptor antagonist, exerts rapid antidepressant effects by enhancing excitatory synaptic strength. These findings suggest that promoting NMDA receptor activation or enhancing NMDA receptor-dependent synaptic potentiation may be an effective strategy for antidepressant treatment.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Behavioral Sciences
Joanna Kowalczyk, Modestos Nakos-Bimpos, Alexia Polissidis, Christina Dalla, Nikolaos Kokras, Krystyna Skalicka-Wozniak, Barbara Budzynska
Summary: This study found that xanthotoxin can reduce depressive behaviors in male mice, while female mice have lower immobility levels compared to males, which may be related to higher levels of serotonin in the female prefrontal cortex. Additionally, xanthotoxin can lead to a dose-dependent increase in serotonin and noradrenaline levels in the female prefrontal cortex.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Neurosciences
Tonghui Su, Yi Lu, Chaoying Fu, Yang Geng, Yelin Chen
Summary: This study demonstrates that the loss of GluN2A in adult mouse brains can elicit strong antidepressant-like responses without causing psychomimetic effects similar to Ketamine. The antidepressant effects of Ketamine and MK-801 are mainly mediated by the suppression of GluN2A rather than GluN2B.
NATURE NEUROSCIENCE
(2023)
Article
Neurosciences
Tonghui Su, Yi Lu, Chaoying Fu, Yang Geng, Yelin Chen
Summary: The study found that the loss of GluN2A in adult mice elicits antidepressant-like responses without causing psychomimetic effects similar to ketamine. The antidepressant effects of ketamine and MK-801 are mediated by the suppression of GluN2A, not GluN2B. Additionally, these drugs increase the excitability of hippocampal neurons through GluN2A.
NATURE NEUROSCIENCE
(2023)
Article
Neurosciences
Yukitoshi Izumi, Fong-Fu Hsu, Charles R. Conway, Peter Nagele, Steven J. Mennerick, Charles F. Zorumski
Summary: Nitrous oxide (N2O) and ketamine have similar hippocampal synaptic enhancement effects and may have therapeutic potential for treatment-resistant major depression.
BIOLOGICAL PSYCHIATRY
(2022)
Article
Pharmacology & Pharmacy
Barbara G. Ferri, Cintia O. de Novais, Raquel S. Bonani, Wellington A. de Barros, Angelo de Fatima, Fabiana C. Vilela, Alexandre Giusti-Paiva
Summary: This study assessed the effect of the psychedelic substances 25HNBOMe and 25H-NBOH on the depressive-like behavior of male adult rats. The results showed that these synthetic psychedelic substances exhibited hallucinogenic effects, and both 25H-NBOMe and 25H-NBOH produced a significantly greater motivation to escape in the forced swimming test. The study provides new insights into the antidepressant properties of a single dose of both 25H-NBOMe and 25H-NBOH.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Clinical Neurology
Agnieszka Palucha-Poniewiera, Karolina Podkowa, Anna Rafalo-Ulinska
Summary: The study demonstrates that the mGlu2/3 receptor antagonist LY341495 has potential in treating depression, and when used in combination with ketamine, it can reduce the effective dose of ketamine and minimize potential side effects.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2021)
Article
Pharmacology & Pharmacy
Pedro Henrique Gobira, Jacob LaMar, Jade Marques, Ariandra Sartim, Kennia Silveira, Luana Santos, Gregers Wegener, Francisco S. Guimaraes, Ken Mackie, Hui-Chen Lu, Samia Joca
Summary: This study investigates the involvement of cannabinoid type 1 receptors (CB1R) in the antidepressant and psychostimulant effects induced by ketamine. The results suggest that CB1R mediate the psychostimulant side effects of ketamine, but do not play a role in its antidepressant properties. Furthermore, pharmacological blockade of CB1R has similar antidepressant effects, but does not potentiate the effects of ketamine.
CANNABIS AND CANNABINOID RESEARCH
(2023)
Article
Multidisciplinary Sciences
Shuangshuang Ma, Min Chen, Yihao Jiang, Xinkuan Xiang, Shiqi Wang, Zuohang Wu, Shuo Li, Yihui Cui, Junying Wang, Yanqing Zhu, Yan Yang, Huan Ma, Shumin Duan, Haohong Li, Yan Yang, Christopher J. Lingle, Hailan Hu
Summary: Ketamine, a potent antidepressant, continues to suppress neuronal firing and block NMDARs in the brain for up to 24 hours after a single injection. This sustained effect is not due to endocytosis, but rather the trapping of ketamine in NMDARs. By modulating the activity of NMDARs, the duration of ketamine action can be controlled, providing new opportunities for therapeutic use of ketamine.
Article
Multidisciplinary Sciences
Shuangshuang Ma, Min Chen, Yihao Jiang, Xinkuan Xiang, Shiqi Wang, Zuohang Wu, Shuo Li, Yihui Cui, Junying Wang, Yanqing Zhu, Yan Zhang, Huan Ma, Shumin Duan, Haohong Li, Yan Yang, Christopher J. Lingle, Hailan Hu
Summary: By manipulating the interactions between the lateral habenula (LHb) and NMDARs, we are able to adjust the duration of ketamine's antidepressant effects in vivo. This study reveals the causal mechanisms behind the sustained antidepressant effects of ketamine and opens up new possibilities for therapeutic use.
Review
Pharmacology & Pharmacy
Lily R. Aleksandrova, Anthony G. Phillips
Summary: The emerging therapeutic efficacy of ketamine and classical psychedelics for depression has sparked considerable interest in the mechanisms underlying neuroplasticity. Preclinical and clinical evidence suggests that these drugs induce synaptic, structural, and functional changes, particularly in pyramidal neurons in the prefrontal cortex, resulting in adaptive rewiring of pathological neurocircuitry.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Ji-Woon Kim, Kanzo Suzuki, Ege T. Kavalali, Lisa M. Monteggia
Summary: Acute administration of (R,S)-ketamine produces rapid and sustained antidepressant effects by blocking NMDA receptors and inducing a novel form of synaptic plasticity in the hippocampus. This triggers downstream signaling events and transcriptional changes that contribute to the antidepressant effects. This review explores the intracellular signaling pathway triggered by ketamine and its connection to synaptic plasticity and sustained antidepressant effects.
TRENDS IN MOLECULAR MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Mohammed H. Elkomy, Fatma I. Abo El-Ela, Randa Mohammed Zaki, Omar A. Alsaidan, Mohammed Elmowafy, Ameeduzzafar Zafar, Khaled Shalaby, Mohamed A. Abdelgawad, Hany A. Omar, Rania Salama, Hussein M. Eid
Summary: This study developed and optimized a drug-loaded thermosensitive gel for intranasal administration to combat depression. The results demonstrated that compared to other formulations, this thermosensitive gel significantly improved behavioral performance and alleviated neural tissue changes in depressed rats. Further research is needed to determine its effectiveness in humans.
Article
Neurosciences
Chrislean Jun Botanas, Raly James Perez Custodio, Hee Jin Kim, June Bryan de la Pena, Leandro Val Sayson, Darlene Mae Ortiz, Mikyung Kim, Hyun Jun Lee, Srijan Acharya, Kyeong-Man Kim, Cheol Jung Lee, Jong Hoon Ryu, Yong Sup Lee, Jae Hoon Cheong
Summary: The study reveals that both S-MXE and R-MXE exhibit antidepressant effects in mice, possibly mediated via glutamatergic and serotonergic mechanisms. R-MXE induces fewer behavioral side effects compared to S-MXE, making it a safer antidepressant option.
Article
Biochemistry & Molecular Biology
Kelly Doolin, Chloe Farrell, Leonardo Tozzi, Andrew Harkin, Thomas Frodl, Veronica O'Keane
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2017)
Article
Immunology
Justin D. Yssel, Eoin O'Neill, Yvonne M. Nolan, Thomas J. Connor, Andrew Harkin
BRAIN BEHAVIOR AND IMMUNITY
(2018)
Article
Psychiatry
Chloe Farrell, Kelly Doolin, Niamh O'Leary, Chaitra Jairaj, Darren Roddy, Leonardo Tozzi, Derek Morris, Andrew Harkin, Thomas Frodl, Zsofia Nemoda, Moshe Szyf, Linda Booij, Veronica O'Keane
PSYCHIATRY RESEARCH
(2018)
Editorial Material
Immunology
Andrew Harkin, Declan M. McLoughlin
BRAIN BEHAVIOR AND IMMUNITY
(2019)
Article
Neurosciences
Eoin O'Neill, Rosa Chiara Goisis, Ruth Haverty, Andrew Harkin
JOURNAL OF NEUROSCIENCE RESEARCH
(2019)
Article
Behavioral Sciences
J. David, S. Gormley, A. L. McIntosh, V. Kebede, G. Thuery, A. Varidaki, E. T. Coffey, A. Harkin
BEHAVIOURAL BRAIN RESEARCH
(2019)
Article
Biochemistry & Molecular Biology
Valentina Ferretti, Federica Maltese, Gabriella Contarini, Marco Nigro, Alessandra Bonavia, Huiping Huang, Valentina Gigliucci, Giovanni Morelli, Diego Scheggia, Francesca Manago, Giulia Castellani, Arthur Lefevre, Laura Cancedda, Bice Chini, Valery Grinevich, Francesco Papaleo
Article
Pharmacology & Pharmacy
Eoin O'Neill, Justin D. Yssel, Caoimhe McNamara, Andrew Harkin
BRITISH JOURNAL OF PHARMACOLOGY
(2020)
Article
Behavioral Sciences
Marianna Leonzino, Luisa Ponzoni, Daniela Braida, Valentina Gigliucci, Marta Busnelli, Ilaria Ceresini, Natalia Duque-Wilckens, Katsuhiko Nishimori, Brian C. Trainor, Mariaelvina Sala, Bice Chini
HORMONES AND BEHAVIOR
(2019)
Article
Neurosciences
Kate O'Reilly, Katherine O'Farrell, Oivind Midttun, Yuliia Rakovets, Jennifer David -Bercholz, Andrew Harkin
Summary: This study demonstrates that brain glia produce neuroactive metabolites via tryptophan-kynurenine catabolism and play a role in reactive glial associated neurodegeneration. Results suggest that inhibiting the kynurenine pathway (KP) metabolites can protect against neuronal atrophy associated with reactive glia.
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
(2021)
Article
Clinical Neurology
Karen M. Ryan, Martha Finnegan, Andrew Harkin, Declan M. McLoughlin
Summary: The study found no significant association between telomerase activity and depression, the therapeutic response to ECT, or exposure to adversity.
EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE
(2021)
Article
Neurosciences
Valentina Gigliucci, Jasper Teutsch, Marc Woodbury-Smith, Mirko Luoni, Marta Busnelli, Bice Chini, Abhishek Banerjee
Summary: The study found that Rett syndrome (RTT) is associated with deficits in KCC2 function and E/I balance. Treatment with recombinant human insulin-like growth factor-1 (rhIGF-1) and oxytocin (OXT) may restore KCC2 expression and normalize E/I balance. These findings provide new therapeutic strategies for RTT.
Editorial Material
Neurosciences
Valentina Gigliucci, Matteo Di Segni, Rossella Ventura, Marco Battaglia
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Neurosciences
Valentina Gigliucci, Marta Busnelli, Francesca Santini, Camilla Paolini, Alessandra Bertoni, Fabienne Schaller, Francoise Muscatelli, Bice Chini
Summary: The neurohormone oxytocin (OXT) is involved in social behavior regulation and is being investigated as a potential therapeutic option for neurodevelopmental disorders. In a mouse model of Schaaf-Yang Syndrome, OXT administration in early postnatal stages rescued autistic-like behavior and cognition. Oxytocin receptor (OXTR) levels were dysregulated in the hippocampus of adult Magel2-KO males, but normalized by OXT treatment. Further analysis showed age, genotype, and OXT treatment effects on OXTR levels in different brain regions.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Pharmacology & Pharmacy
Rebecca Maher, Almudena Moreno-Borrallo, Dhruvi Jindal, Binh T. Mai, Eduardo Ruiz-Hernandez, Andrew Harkin
Summary: Nanomedicine focuses on developing nanocarriers to improve drug delivery to the brain for the treatment of neuropsychiatric disorders and neurological diseases. Polymer and lipid-based drug carriers have advantages in delivering drugs to the central nervous system (CNS) due to their safety, drug loading capacity, and controlled release properties. These carriers have shown potential in penetrating the blood-brain barrier (BBB) and have been extensively studied in glioblastoma, epilepsy, and neurodegenerative disease models. Intranasal administration has emerged as an attractive route to bypass the BBB using tailored nanocarriers. This review explores the characteristics of polymeric and lipid-based nanocarriers and their potential for CNS drug repurposing, as well as the progress in intranasal drug delivery for neurological diseases.