Article
Biochemistry & Molecular Biology
Orr Shahar, Alexander Botvinnik, Noam Esh-Zuntz, Michal Brownstien, Rachel Wolf, Amit Lotan, Gilly Wolf, Bernard Lerer, Tzuri Lifschytz
Summary: There is growing interest in the therapeutic potential of psilocybin. This study examined the role of different serotonergic receptors and TAAR1 in modulating the head twitch response induced by 5-HTP and psilocybin in mice. The findings suggest that compounds that modulate psychedelic-induced head twitch response may have important therapeutic potential.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Anat Levit Kaplan, Danielle N. Confair, Kuglae Kim, Ximena Barros-Alvarez, Ramona M. Rodriguiz, Ying Yang, Oh Sang Kweon, Tao Che, John D. McCorvy, David N. Kamber, James P. Phelan, Luan Carvalho Martins, Vladimir M. Pogorelov, Jeffrey F. DiBerto, Samuel T. Slocum, Xi-Ping Huang, Jain Manish Kumar, Michael J. Robertson, Ouliana Panova, Alpay B. Seven, Autumn Q. Wetsel, William C. Wetsel, John J. Irwin, Georgios Skiniotis, Brian K. Shoichet, Bryan L. Roth, Jonathan A. Ellman
Summary: Researchers successfully screened and synthesized molecules that can activate the 5-HT2A receptor using structure-based docking and optimization methods. These molecules exhibited potent antidepressant activity in mouse models without psychedelic effects.
Article
Chemistry, Medicinal
Christian B. M. Poulie, Eline Pottie, Icaro A. Simon, Kasper Harpsoe, Laura D'Andrea, Igor V. Komarov, David E. Gloriam, Anders A. Jensen, Christophe P. Stove, Jesper L. Kristensen
Summary: This study evaluated the biased signaling of the 5-HT2AR receptor and found that the interaction with Ser159(3x36) is crucial for signaling and efficacy. G alpha(q)-mediated signaling was more affected. These findings contribute to the development of more effective 5-HT2AR agonists.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Neurosciences
Arya Rahbarnia, Zhaoxia Li, Paul J. Fletcher
Summary: This study aimed to evaluate the impact of psilocybin on attention and compare it with 5-HT2A receptor agonists and antagonists. The findings suggest that psilocybin and other drugs impaired performance in mice during a task, but this may be partially due to the effects of the drugs on locomotor activity.
PSYCHOPHARMACOLOGY
(2023)
Article
Behavioral Sciences
Anna U. Odland, Jesper L. Kristensen, Jesper T. Andreasen
Summary: This study confirmed that psychedelics acting as 5-HT2AR agonists can reduce compulsive-like digging behavior in mice, while also suggesting that both 5-HT2A and 5-HT(2C)Rs may work in parallel on this behavior. Results with psilocybin indicate that a 5-HT2R-independent mechanism may also contribute to its effect on repetitive digging behavior.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Medicine, Research & Experimental
I Erkizia-Santamaria, R. Alles-Pascual, I Horrillo, J. J. Meana, J. E. Ortega
Summary: The study found that psilocin showed similar affinities for 5HT2AR, 5HT2CR, and 5HT1AR in both human and mice brain. Psilocybin induced a dose-dependent head-twitch response (HTR) and affected body temperature, which were both mediated by 5HT2AR, 5HT2CR, and 5HT1AR. These findings provide key insights into the mechanism of action of psilocybin and its therapeutic effects.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Gavin P. Schmitz, Manish K. Jain, Samuel T. Slocum, Bryan L. Roth
Summary: In this study, the researchers examined the effects of sequence variations in the 5-HT2AR gene on the signaling of four commonly used psychedelic drugs. They found that these genetic variations have statistically significant, but modest, effects on the efficacy and potency of the drugs. Importantly, these effects are specific to each drug.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Gavin P. Schmitz, Manish K. Jain, Samuel T. Slocum, Bryan L. Roth
Summary: Sequence variations in the 5-HT2AR gene have been found to have modest but statistically significant effects on the efficacy and potency of commonly used psychedelic drugs. The in vitro pharmacological effects of these variations are specific to each drug.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Pharmacology & Pharmacy
Yi Jiang, Jie Zhou, Bai-Lin Song, Yan Wang, Dong-Lin Zhang, Zheng-Tian Zhang, Lai-Fu Li, Ying-Juan Liu
Summary: Social animals self-organize into dominance hierarchies, influenced by the serotonin system in the amygdala. This study explores the role of different 5-HT receptor subtypes in social rank determination and reveals their involvement in the formation and modulation of social hierarchy.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Hirohito Esaki, Yuki Sasaki, Naoya Nishitani, Hikari Kamada, Satoko Mukai, Yoshitaka Ohshima, Sao Nakada, Xiyan Ni, Satoshi Deyama, Katsuyuki Kaneda
Summary: This study examined whether the prosocial effects induced by MDMA are mediated by 5-HT neurotransmission in the medial prefrontal cortex (mPFC) and the basolateral nucleus of amygdala (BLA). The results showed that selective inhibition of 5-HT transporters before MDMA administration did not suppress the prosocial effects. However, the 5-HT1A receptor antagonist WAY100635 significantly suppressed the prosocial effects of MDMA. Furthermore, local administration of WAY100635 into the BLA, but not the mPFC, suppressed the MDMA-induced prosocial effects. These findings suggest that MDMA induces prosocial effects through the stimulation of 5-HT1A receptors in the BLA.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Review
Behavioral Sciences
Manesh Girn, Fernando E. Rosas, Richard E. Daws, Courtney L. Gallen, Adam Gazzaley, Robin L. Carhart-Harris
Summary: Recent findings suggest that psychedelic-assisted therapy may have transdiagnostic efficacy, but a deeper understanding of the effects on the brain is needed. Functional neuroimaging studies have shown that psychedelics reduce the segregation of brain networks, but results have been inconsistent. This article argues for a perspective based on complexity science to explain these inconsistencies, highlighting the distributed, interactional, and dynamic nature of brain function. It proposes that psychedelics induce a more dynamically flexible, diverse, integrated, and information-sharing mode of brain function, consistent with greater criticality. This 'meta' perspective has the potential to unify previous findings and guide the development of mechanistic models.
TRENDS IN COGNITIVE SCIENCES
(2023)
Article
Chemistry, Medicinal
Edward Ofori, Edem K. Onyameh, Uma M. Gonela, Chandrashekhar Voshavar, Barbara Bricker, Tracy L. Swanson, Amy J. Eshleman, Jennifer L. Schmachtenberg, Shelley H. Bloom, Aaron J. Janowsky, Seth Y. Ablordeppey
Summary: We have conducted a study to explore the potential of dual 5-HT1AR and 5-HT7R ligands, resulting in the identification of a new compound with high affinity for these receptors. This compound, designated as 21, shows promising functional characteristics as a potential antidepressant agent.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Johannes Morstein, Giovanna Romano, Belinda E. Hetzler, Ambrose Plante, Caleb Haake, Joshua Levitz, Dirk Trauner
Summary: This study develops tools for optical control of serotonin receptors, providing a new method for studying receptor function. By constructing a repeatable and reversible optical control system, this study lays the foundation for extending photopharmacology to the serotonin receptor family.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Behavioral Sciences
Paloma Molina Hernandes, Matheus Fitipaldi Batistela, Heloisa Helena Vilela-Costa, Ana Beatriz Sant 'Ana, Vinicius Dias Kumpel, Mariane Cariati Tirapelle, Ariela de Oliveira Pedro Bom, Telma Goncalves Carneiro Spera de Andrade, Helio Zangrossi Jr
Summary: Changes in 5-HT1A receptor-mediated neurotransmission in the hippocampus are associated with anxiety, depression, and the action of antidepressant drugs. Studies have shown that 5-HT1ARs in the ventral pole play a tonic inhibitory role in anxiety processing, while not being involved in regulating panic-related escape behavior.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Neurosciences
Matthieu Colom, Benjamin Vidal, Sylvain Fieux, Jerome Redoute, Nicolas Costes, Franck Lavenne, Ines Merida, Zacharie Irace, Thibaud Iecker, Caroline Bouillot, Thierry Billard, Adrian Newman-Tancredi, Luc Zimmer
Summary: The study evaluated the sensitivity of the radiopharmaceutical [F-18]F13640 to endogenous serotonin release, demonstrating its effectiveness in measuring neurotransmitter fluctuations but highlighting the importance of longer PET scans for accurate displacement measurements.
FRONTIERS IN NEUROSCIENCE
(2021)
