Hallucinogens Recruit Specific Cortical 5-HT2A Receptor-Mediated Signaling Pathways to Affect Behavior

@article{GonzlezMaeso2007HallucinogensRS,
  title={Hallucinogens Recruit Specific Cortical 5-HT2A Receptor-Mediated Signaling Pathways to Affect Behavior},
  author={Javier Gonz{\'a}lez-Maeso and Noelia V. Weisstaub and Mingming Zhou and Pokman Chan and Lidija Ivi{\'c} and Rosalind L. Ang and Alena Lira and Maria Bradley-Moore and Yongchao Ge and Qiang Zhou and Stuart C. Sealfon and Jay A Gingrich},
  journal={Neuron},
  year={2007},
  volume={53},
  pages={439-452}
}
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 poorly understood. By genetically expressing 2AR only in cortex, we show that 2AR-regulated pathways on… Expand
Agonist-directed signaling of the serotonin 2A receptor depends on β-arrestin-2 interactions in vivo
TLDR
This study suggests that the 5-HT2AR–β-arrestin interaction may be particularly important in receptor function in response to endogenous serotonin levels, which could have major implications in drug development for treating neuropsychiatric disorders such as depression and schizophrenia. Expand
Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens
TLDR
The evidence demonstrating that the effects of indoleamine hallucinogens in a variety of animal behavioral paradigms are mediated by both 5-HT(2) and non-5-HT (2) receptors is reviewed. Expand
Hallucinogens induce a specific barcode of phosphorylation on the serotonin2A receptor that underlies a weaker receptor desensitization and internalization
The serotonin (5-Hydroxytryptamine, 5-HT) 2A receptor represents one of the most striking examples where functional selectivity (or ligand-biased signaling) is transduced in distinct behaviours. ThisExpand
Hallucinogenic 5-hydroxytryptamine 2A receptor agonist effects in senescence-accelerated mice.
TLDR
Results indicate that SAMP6 increases DOI-dependent ERK1/2-CREB signaling leading to more head-twitch responses than SAMR1, and that Samp6 could provide a useful model for examining the relationship between 5-HT2AR regulatory signaling and behavioral phenotypes. Expand
D-serine deficiency attenuates the behavioral and cellular effects induced by the hallucinogenic 5-HT2A receptor agonist DOI
TLDR
Findings suggest that D-serine-dependent NMDAR activity is involved in mediating the cellular and behavioral effects of 5-HT2AR activation. Expand
Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex
TLDR
The results from these experiments do not support the idea that 5-HT2ARs elicit the release of an excitatory retrograde messenger nor that they activate thalamocortical afferents, the two dominant hypotheses, and suggest that5-HT 2ARs facilitate intrinsic networks within the PFC. Expand
Chronic Phenethylamine Hallucinogen Treatment Alters Behavioral Sensitivity to a Metabotropic Glutamate 2/3 Receptor Agonist
TLDR
It was discovered that the repeated dosing regimen required for discrimination training attenuated the behavioral effects of the mGlu2/3 receptor agonist LY379268, and chronic studies confirmed that repeated hallucinogen treatment causes a loss of behavioral activity of mGglutamatergic receptors. Expand
Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways.
TLDR
Recent advances in understanding hallucinogen drug action are reviewed through characterization of structure, neuroanatomical location, and function of the 5-HT2A receptor. Expand
Serotonin and serotonin receptors in hallucinogen action
Abstract Hallucinogens (psychedelics) are substances that induce profound changes in perception and cognition. The closely related 3,4-methylenedioxymethamphetamine (MDMA) produces euphoria and aExpand
The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens
TLDR
It is argued that activation of 5-HT2C receptors on NAc shell, GABAergic, medium spiny neurons inhibits potassium Kv1.x channels, thereby enhancing inhibitory activity via intrinsic mechanisms and providing a potential reason for the non-addictive nature of classic hallucinogens. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 75 REFERENCES
Transcriptome Fingerprints Distinguish Hallucinogenic and Nonhallucinogenic 5-Hydroxytryptamine 2A Receptor Agonist Effects in Mouse Somatosensory Cortex
TLDR
The results demonstrate that chemicals acting at the 5-HT2AR induce specific cellular response patterns in vivo that are reflected in unique changes in the somatosensory cortex transcriptome. Expand
Lysergic acid diethylamide-induced Fos expression in rat brain: role of serotonin-2A receptors
TLDR
The results indicate that the LSD activation of medial prefrontal cortex and anterior cingulate cortex is mediated by 5- HT(2A) receptors, whereas in amygdala 5-HT( 2A) receptor activation is a component of the response. Expand
A major role for thalamocortical afferents in serotonergic hallucinogen receptor function in the rat neocortex
TLDR
These experiments demonstrate that activation of cortical 5-HT(2A) receptors modulates transmitter release from thalamocortical terminals, and unexpectedly, lesioning theThalamic lesions also alters 5- HT( 2A) receptor binding in the prefrontal cortex. Expand
Agonist activity of LSD and lisuride at cloned 5HT2A and 5HT2C receptors
TLDR
Results indicate that lisuride may possess hallucinogenic activity, although the psychopharmacological effects of l isuride appear to be different from the hallucinationsinogenic effects of LSD. Expand
Re-evaluation of lisuride pharmacology: 5-hydroxytryptamine1A receptor-mediated behavioral effects overlap its other properties in rats
TLDR
It is demonstrated that the behavioral effects of low doses of lisuride are clearly mediated by stimulation of 5-HT1A receptors. Expand
5-Hydroxytryptamine2-family receptors (5-hydroxytryptamine2A, 5-hydroxytryptamine2B, 5-hydroxytryptamine2C): where structure meets function.
TLDR
Results suggest that discrete domains of the receptor structure are important for ligand binding, G-protein coupling, and internalization, as well as a model for regulation of 5-HT2-family receptors by receptor-mediated endocytosis. Expand
Effector pathway-dependent relative efficacy at serotonin type 2A and 2C receptors: evidence for agonist-directed trafficking of receptor stimulus.
TLDR
Concentration-response curves to 5-HT2C agonists were fit well by a three-state model of receptor activation, suggesting that two active receptor states may be sufficient to explain pathway-dependent agonist efficacy. Expand
The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs I: Antagonist correlation analysis
TLDR
The data indicate that the stimulus effects of LSD, and the substitution of (−)DOM for the LSD stimulus are mediated by agonist activity at 5-HT2A receptors. Expand
Localization of 5-HT2A receptors on dopamine cells in subnuclei of the midbrain A10 cell group
TLDR
An anatomical basis is provided for the physiological modulation of dopamine neurons in the rostral ventral tegmental area either directly, by 5-HT(2A) receptors localized on dopamine cells, or indirectly, through a non-dopaminergic mechanism. Expand
Effects of lisuride and LSD on cerebral monoamine systems and hallucinosis
TLDR
The present findings do not support the hypothesis that the hallucinogenic effect of LSD is reflected by variations in the level and turnover of the brain amines, and a stimulation of 5-HT autoreceptors is also evident after the non-hallucinogenic lisuride. Expand
...
1
2
3
4
5
...