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Distinct 5-HT receptor subtypes regulate claustrum excitability by serotonin and the psychedelic, DOI
Tanner L Anderson1, Jack V Keady2, Judy Songrady2
1University of Kentucky, College of Medicine, Department of Neuroscience, Lexington, KY 40536, United States.
Progress in Neurobiology
|September 1, 2024
Summary
Serotonin (5-HT) receptors in the claustrum (CLA) regulate responses to psychedelics. The 5-HT2C receptor, not 5-HT2A, mediates these effects on CLA-ACC circuit activity.
Area of Science:
- Neuroscience
- Neuropharmacology
- Molecular Biology
Background:
- The claustrum (CLA) plays a role in psychedelic responses.
- Serotonin (5-HT) receptors are key targets for psychedelic drugs.
- CLA's interaction with serotonin receptors is not well understood.
Purpose of the Study:
- To investigate the expression of serotonin receptor subtypes in the CLA.
- To determine the effects of serotonin and psychedelics on CLA neuronal excitability.
- To elucidate the specific serotonin receptor subtypes involved in CLA responses to psychedelics.
Main Methods:
- Characterized CLA expression of all known 5-HT receptor subtypes.
- Performed electrophysiological recordings on cortical-projecting CLA neurons.
- Applied 5-HT and DOI (a psychedelic) and assessed effects on synaptic currents.
Main Results:
- CLA is enriched with 5-HT2C receptors, primarily on glutamatergic neurons.
- 5-HT inhibits, while DOI stimulates, excitatory postsynaptic currents (EPSCs) in CLA-ACC neurons.
- Inhibition of 5-HT2C receptors, not 5-HT2A, reversed both 5-HT and DOI effects.
Conclusions:
- Specific 5-HT receptor subtypes regulate CLA excitability.
- 5-HT2C receptors, not 5-HT2A, are critical for psychedelic drug action in the CLA-ACC circuit.
- Challenges the established role of 5-HT2A in psychedelic-induced glutamatergic responses within this circuit.
Keywords:
2,5-dimethoxy-4-iodoamphetamine (DOI)5-HT2A5-HT2CClaustrumElectrophysiologyPsychedelicsSerotoninMore Related Videos
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