Scientific Reports
October 3, 2019
Mario de la Fuente Revenga, Jong M. Shin, Hiba Z. Vohra et al.
57 citations
Abstract Head-twitch behavior (HTR) is the behavioral signature of psychedelic drugs upon stimulation of the serotonin 5-HT 2A receptor (5-HT 2A R) in rodents. Following the previous report of a semi-automated detection of HTR based on the dynamics of mouse’s head movement, here we present a system for the identification of individual HTR events in a fully automated fashion. The validity of...
Psychopharmacology
November 2018
Kelsey S. Hideshima, Ashkhan Hojati, Justin M. Saunders et al.
Serotonin 5-HT2A and metabotropic glutamate 2 (mGlu2) are neurotransmitter G protein-coupled receptors (GPCRs) involved in the signaling mechanisms underlying psychosis and schizophrenia treatment. Previous findings in mGlu2 knockout (KO) mice suggested that mGlu2 is necessary for head-twitch behavior, a rodent phenotype characteristic of hallucinogenic 5-HT2A receptor agonists. However, the...
Current Topics in Behavioral Neurosciences
2017
Juan F López-Giménez, Javier González-Maeso
302 citations
The neuropsychological effects of naturally occurring psychoactive chemicals have been recognized for millennia. Hallucinogens, which include naturally occurring chemicals such as mescaline and psilocybin, as well as synthetic compounds, such as lysergic acid diethylamide (LSD), induce profound alterations of human consciousness, emotion, and cognition. The discovery of the hallucinogenic...
Journal of Visualized Experiments
July 9, 2016
Terrell Holloway, José L. Moreno, Javier González-Maeso
The heteromeric receptor complex between 5-HT2A and mGlu2 has been implicated in some of the behavioral phenotypes in mouse models of psychosis(1,2). Consequently, investigation of structural details of the interaction between 5-HT2A and mGlu2 affecting schizophrenia-related behaviors represents a powerful translational tool. As previously shown, the head-twitch response (HTR) in mice is...
Pflügers Archiv: European Journal of Physiology
January 16, 2016
Lia Baki, M. Fribourg, Jason Younkin et al.
We previously reported that co-expression of the Gi-coupled metabotropic glutamate receptor 2 (mGlu2R) and the Gq-coupled serotonin (5-HT) 2A receptor (2AR) in Xenopus oocytes (Fribourg et al. Cell 147:1011–1023, 2011) results in inverse cross-signaling, where for either receptor, strong agonists suppress and inverse agonists potentiate the signaling of the partner receptor. Importantly,...
The International Journal of Neuropsychopharmacology
June 10, 2013
José L. Moreno, Javier González-Maeso
30 citations
Abstract One of the main obstacles faced by translational neuroscience is the development of animal models of psychiatric disorders. Behavioural pharmacology studies indicate that psychedelic drugs, such as lysergic acid diethylamide (LSD) and dissociative drugs, such as phencyclidine (PCP), induce in healthy human volunteers psychotic and cognitive symptoms that resemble some of those observed...
Neuropsychopharmacology
May 24, 2013
Michael B. Gatch, Alexey Kozlenkov, Ren-Qi Huang et al.
Anecdotal reports have surfaced concerning misuse of the HIV antiretroviral medication efavirenz ((4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one) by HIV patients and non-infected teens who crush the pills and smoke the powder for its psychoactive effects. Molecular profiling of the receptor pharmacology of efavirenz pinpointed interactions with...
Journal of Neuroscience
January 16, 2013
Terrell Holloway, José L. Moreno, Adrienne Umali et al.
122 citations
It has been suggested that severe adverse life events during pregnancy increase the risk of schizophrenia in the offspring. The serotonin 5-HT 2A and the metabotropic glutamate 2 (mGlu2) receptors both have been the target of considerable attention regarding schizophrenia and antipsychotic drug development. We tested the effects of maternal variable stress during pregnancy on expression and...
Neuroscience Letters
January 16, 2013
José L. Moreno, Terrell Holloway, Vinayak Rayannavar et al.
44 citations
Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT(2A) receptor. Metabotropic glutamate 2/3 (mGlu2/3) receptor ligands show efficacy in modulating the cellular and behavioral responses induced by hallucinogenic drugs. Here, we explored...
ACS Chemical Neuroscience
September 24, 2012
James B. Hanks, Javier González-Maeso
152 citations
The serotonin 5-HT(2A) receptor is the major target of psychedelic drugs such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Serotonergic psychedelics induce profound effects on cognition, emotion, and sensory processing that often seem uniquely human. This raises questions about the validity of animal models of psychedelic drug action. Nonetheless, recent findings suggest...
Psychopharmacology
July 28, 2012
J. Moreno, Terrell Holloway, Adrienne Umali et al.
In schizophrenia patients, optimal treatment with antipsychotics requires weeks to months of sustained drug therapy. However, single administration of antipsychotic drugs can reverse schizophrenia-like behavioral alterations in rodent models of psychosis. This raises questions about the physiological relevance of such antipsychotic-like activity. This study evaluates the effects of chronic...
Journal of Neuroscience
February 2, 2011
José L. Moreno, Mitsumasa Kurita, Terrell Holloway et al.
122 citations
Epidemiological studies indicate that maternal influenza viral infection increases the risk for schizophrenia in the adult offspring. The serotonin and glutamate systems are suspected in the etiology of schizophrenia, as well as in the mechanism of action of antipsychotic drugs. The effects of hallucinogens, such as psilocybin and mescaline, require the serotonin 5-HT 2A receptor, and induce...
Trends in Neurosciences
April 1, 2009
Javier González-Maeso, Stuart C. Sealfon
Research on psychedelics such as lysergic acid diethylamide (LSD) and dissociative drugs such as phencyclidine (PCP) and the symptoms, neurochemical abnormalities and treatment of schizophrenia have converged. The effects of hallucinogenic drugs resemble some of the core symptoms of schizophrenia. Some atypical antipsychotic drugs were identified by their high affinity for serotonin 5-HT(2A)...
Current Medicinal Chemistry
March 1, 2009
Javier González-Maeso, Stuart C. Sealfon
74 citations
Seven transmembrane domain receptors, also termed G protein-coupled receptors (GPCRs), represent the most common molecular target for therapeutic drugs. The generally accepted pharmacological model for GPCR activation is the ternary complex model, in which GPCRs exist in a dynamic equilibrium between the active and inactive conformational states. However, the demonstration that different...
Nature
March 6, 2008
Javier González-Maeso, Rosalind L Ang, Tony Yuen et al.
The psychosis associated with schizophrenia is characterized by alterations in sensory processing and perception. Some antipsychotic drugs were identified by their high affinity for serotonin 5-HT2A receptors (2AR). Drugs that interact with metabotropic glutamate receptors (mGluR) also have potential for the treatment of schizophrenia. The effects of hallucinogenic drugs, such as psilocybin and...
Neuron
February 1, 2007
Javier González-Maeso, Noelia V Weisstaub, Mingming Zhou et al.
Hallucinogens, including mescaline, psilocybin, and lysergic acid diethylamide (LSD), profoundly affect perception, cognition, and mood. All known drugs of this class are 5-HT(2A) receptor (2AR) agonists, yet closely related 2AR agonists such as lisuride lack comparable psychoactive properties. Why only certain 2AR agonists are hallucinogens and which neural circuits mediate their effects are...
Journal of Neuroscience
October 1, 2003
Javier González-Maeso, Tony Yuen, Barbara J. Ebersole et al.
295 citations
Most neuropharmacological agents and many drugs of abuse modulate the activity of heptahelical G-protein-coupled receptors. Although the effects of these ligands result from changes in cellular signaling, their neurobehavioral activity may not correlate with results of in vitro signal transduction assays. 5-Hydroxytryptamine 2A receptor (5-HT2AR) partial agonists that have similar...