Current topics in behavioral neurosciences
January 1, 2017
Juan F. López‐giménez, Javier González‐maeso
302 citations
Hallucinogens such as mescaline, psilocybin, and LSD profoundly alter consciousness, emotion, and cognition. Their discovery, particularly LSD's similarity to serotonin, suggested that biogenic amines like serotonin are involved in mental disorders such as schizophrenia. Although hallucinogens bind to multiple G protein-coupled receptor subtypes, their key effects involve agonist activity at the serotonin 5-HT2A receptor. This chapter reviews recent advances in understanding hallucinogen action by characterizing the structure, neuroanatomical location, and function of the 5-HT2A receptor.
Journal of Neuroscience
October 1, 2003
Javier González‐maeso, Tony Yuen, Barbara J. Ebersole et al.
295 citations
Different drugs that activate the same serotonin receptor (5-HT2AR) can produce distinct patterns of gene expression in the brain, which correspond to different behavioral effects. The hallucinogens DOI and LSD triggered a head-twitch response in mice and produced similar changes in the somatosensory cortex transcriptome, while the nonhallucinogenic drug lisuride did not cause this behavior and generated a different transcriptome fingerprint. These effects were absent in mice lacking the 5-HT2AR, confirming the receptor's role. The findings suggest that drugs acting at the same receptor can induce unique cellular response patterns in the living brain, detectable through transcriptome analysis.
ACS Chemical Neuroscience
September 24, 2012
James B. Hanks, Javier González‐maeso
152 citations
The serotonin 5-HT(2A) receptor is the primary target of psychedelic drugs like LSD, mescaline, and psilocybin. These substances produce profound changes in cognition, emotion, and sensory processing that seem uniquely human, raising questions about the validity of animal models. However, recent research indicates that behavioral abnormalities induced by psychedelics in rodents can predict effects in humans. This review examines the behavioral effects of psychedelic drugs in rodent models, evaluates the translational potential of these findings, and identifies areas needing further research to clarify the molecular mechanisms and neural circuits underlying their neuropsychological effects.
Journal of Neuroscience
January 16, 2013
Terrell Holloway, José L. Moreno, Adrienne Umali et al.
122 citations
Severe stress during pregnancy in mice alters the expression of two brain receptors linked to schizophrenia: serotonin 5-HT2A increases and metabotropic glutamate mGlu2 decreases in the frontal cortex. These changes correspond to behavioral differences in adult offspring, such as a heightened response to a hallucinogenic drug and reduced antipsychotic-like effects of a mGlu2/3 agonist. Cross-fostering ruled out maternal care as a cause, and similar effects appeared after prenatal immune activation. The findings support the idea that early neurodevelopmental disruptions contribute to schizophrenia risk.
Journal of Neuroscience
February 2, 2011
José L. Moreno, Mitsumasa Kurita, Terrell Holloway et al.
122 citations
Maternal infection with influenza virus in mice alters the expression of serotonin and glutamate receptors in the frontal cortex of adult offspring, leading to behavioral changes relevant to schizophrenia. The 5-HT 2A receptor is upregulated and the mGlu 2 receptor is downregulated. Offspring show increased head-twitch responses to hallucinogens and reduced antipsychotic-like effects of a glutamate agonist, along with altered signaling pathways. These findings suggest a biochemical link between prenatal viral infection and schizophrenia-related behaviors, potentially guiding new treatments.
Neuroscience Letters
January 16, 2013
José L. Moreno, Terrell Holloway, Vinayak Rayannavar et al.
44 citations
Hallucinogenic drugs like LSD, mescaline, and psilocybin all bind strongly to the serotonin 5-HT(2A) receptor. Drugs that affect metabotropic glutamate 2/3 (mGlu2/3) receptors can alter the cellular and behavioral effects of hallucinogens. In mice, chronic treatment (21 days) with the mGlu2/3 receptor antagonist LY341495 (1.5 mg/kg) reduced the hallucinogenic-like effects of LSD (0.24 mg/kg). This treatment decreased binding of a radiolabeled tracer to 5-HT(2A) receptors in the somatosensory cortex of normal mice, but not in mice lacking the mGlu2 receptor. It also reduced head-twitch behavior and the expression of certain genes (c-fos, egr-1, egr-2) that are normally triggered by hallucinogenic drugs. These results suggest that repeatedly blocking mGlu2 receptors dampens the 5-HT(2A) receptor-mediated effects of LSD.
The International Journal of Neuropsychopharmacology
June 10, 2013
José L. Moreno, Javier González‐maeso
30 citations
Psychedelic drugs like LSD and dissociative drugs like PCP produce psychotic and cognitive symptoms in healthy people that resemble aspects of schizophrenia. Serotonin 5-HT2A and metabotropic glutamate 2 receptors are involved in how these drugs work. This review examines recent studies using LSD-like and PCP-like drugs in rodents that link these receptors to the biology of schizophrenia and its treatment.
Journal of Neurochemistry
November 6, 2021
Alaina M. Jaster, Mario de la Fuente Revenga, Javier González‐maeso
28 citations
Psychedelic research is accelerating across disciplines and biological levels. Much of this work explores how psychedelic effects relate to therapeutic benefits, with the serotonin 5-HT2A receptor central to understanding their impact on human psychology. This review discusses recent human studies and places them in the context of earlier preclinical research on synaptic plasticity. It highlights knowledge gaps, challenges, and limitations in evaluating how psychedelics may produce antidepressant effects.
bioRxiv (Cold Spring Harbor Laboratory)
February 25, 2021
Mario de la Fuente Revenga, Bohan Zhu, Christopher A. Guevara et al.
11 citations
preprint
A single dose of the psychedelic DOI produces rapid and sustained antidepressant-like effects by altering chromatin organization at enhancer regions of genes involved in synaptic assembly in the frontal cortex, an effect mediated by the 5-HT2A receptor. These epigenetic changes drive lasting synaptic plasticity and accelerate fear extinction. The findings suggest that epigenetic-driven synaptic plasticity underlies psychedelics' long-lasting antidepressant action, but also indicate potential risks for individuals with underlying vulnerability to psychosis, as the altered neuronal epigenome overlapped with genetic loci associated with schizophrenia, depression, and attention deficit hyperactivity disorder.
Research Square (Research Square)
July 7, 2023
Rika Takaba, Daisuke Ibi, Keisuke Yoshida et al.
4 citations
Serotonergic psychedelics like psilocin, DOI, and TCB-2 produce antidepressant-like effects in mice by activating the serotonin 5-HT2A receptor. Mice given a single injection of these drugs showed less immobility in the forced swimming and tail-suspension tests 24 hours later, effects blocked by a 5-HT2A antagonist. The antidepressant-like effect of psilocin lasted at least three weeks. However, only psilocin reduced anxiety-like behavior in the novelty-suppressed feeding test, and this effect was not blocked by the 5-HT2A antagonist. The drugs did not alter spontaneous movement or head-twitch responses. The findings indicate 5-HT2A mediates antidepressant but not anxiolytic effects of these psychedelics.
Journal of Pain
April 1, 2024
M. Imad Damaj, Eda Köşeli, Belle Buzzi et al.
2 citations
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