DOI-Induced Activation of the Cortex: Dependence on 5-HT2AHeteroceptors on Thalamocortical Glutamatergic Neurons
Jennifer L. Scruggs, Sachin Patel, Michael Bubser, Ariel Y. Deutch
Journal of Neuroscience December 1, 2000 DOI: 10.1523/jneurosci.20-23-08846.2000 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rat |
| Interventions | DOI MDL 100 907 SB 206 553 GYKI 52466 |
| Topics | Addiction Serotonin |
| Keywords | Glutamatergic Ampa receptor Thalamus Somatosensory system Cortex anatomy Glutamate receptor Cerebral cortex Antagonist C-fos Gene expression Biochemistry |
| Citations | 154 |
| Key findings | DOI acts through 5-HT2A receptors on thalamocortical neurons to increase glutamate release, which drives cortical Fos expression via AMPA receptors. |
Abstract
Administration of the hallucinogenic 5-HT 2A/2C agonist 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) induces expression of Fos protein in the cerebral cortex. To understand the mechanisms subserving this action of DOI, we examined the consequences of pharmacological and surgical manipulations on DOI-elicited Fos expression in the somatosensory cortex of the rat. DOI dose-dependently increased cortical Fos expression. Pretreatment with the selective 5-HT 2A antagonist MDL 100,907 completely blocked DOI-elicited Fos expression, but pretreatment with the 5-HT 2C antagonist SB 206,553 did not modify DOI-elicited Fos expression. These data suggest that DOI acts through 5-HT 2A receptors to increase cortical Fos expression. However, we found that DOI did not induce Fos in cortical 5-HT 2A immunoreactive neurons but did increase expression in a band of neurons spanning superficial layer V to deep III, within the apical dendritic fields of layer V 5-HT 2A -immunoreactive cells. This band of Fos immunoreactive neurons was in register with anterogradely labeled axons from the ventrobasal thalamus, which have previously been shown to be glutamatergic and express the 5-HT 2A transcript. The effects of DOI were markedly reduced in animals pretreated with the AMPA/KA antagonist GYKI 52466, and lesions of the ventrobasal thalamus attenuated DOI-elicited Fos expression in the cortex. These data suggest that DOI activates 5-HT 2A receptors on thalamocortical neurons and thereby increases glutamate release, which in turn drives Fos expression in cortical neurons through an AMPA receptor-dependent mechanism. These data cast new light on the mechanisms of action of hallucinogens.
Comparable studies
Other experimental studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Healthy human volunteers | 1998 | Experimental study | |
| Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | 2000 | Experimental study | |
| Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Rat brain | 1988 | Experimental study | |
| The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Human platelet plasma membrane vesicles and bovine adrenal chromaffin granule membrane... | 1992 | Laboratory study | |
| 5-HT2AReceptor-Mediated Regulation of Brain-Derived Neurotrophic Factor mRNA in the Hippocampus and the Neocortex Rat brain | 1997 | Experimental study |
Citations in the library
Cited by 53
- Control of Serotonergic Function in Medial Prefrontal Cortex by Serotonin-2A Receptors through a Glutamate-Dependent Mechanism Journal of Neuroscience December 15, 2001
- Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways Current Topics in Behavioral Neurosciences 2017
- Transcriptome Fingerprints Distinguish Hallucinogenic and Nonhallucinogenic 5-Hydroxytryptamine 2A Receptor Agonist Effects in Mouse Somatosensory Cortex Journal of Neuroscience October 1, 2003
- Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin. Neuropsychopharmacology November 1, 2020
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
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Cites 11
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Reversal of Phencyclidine Effects by a Group II Metabotropic Glutamate Receptor Agonist in Rats Science August 28, 1998
- Serotonin, via 5-HT2A receptors, increases EPSCs in layer V pyramidal cells of prefrontal cortex by an asynchronous mode of glutamate release Brain Research April 1, 1999
- Agonist Properties of N,N-Dimethyltryptamine at Serotonin 5-HT2A and 5-HT2C Receptors Pharmacology, Biochemistry, and Behavior November 1, 1998
- Characterization of the Discriminative Stimulus Properties Induced by 5‐HT1and 5‐HT2Agonists in Rats Pharmacology & Toxicology February 1, 1989
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