The effects of serotonergic psychedelics in synaptic and intrinsic properties of neurons in layer II/III of the orbitofrontal cortex.
Zi-Hang Tang, Zhi-Peng Yu, Qiong Li, Xiao-Qin Zhang, Kadeliya Muhetaer, Zheng-Chun Wang, Peng Xu, Hao-Wei Shen
Psychopharmacology June 1, 2023 DOI: 10.1007/s00213-023-06366-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Ex vivo electrophysiology study Peer reviewed |
|---|---|
| Population | Acute brain slices from adult male Sprague Dawley rats |
| Intervention | 25C-NBOMe |
| Topics | Serotonin |
| Keywords | Excitation/inhibition balance Orbitofrontal cortex Psychedelics |
| Citations | 7 |
| Key points | 25C-NBOMe promotes local excitation/inhibition ratios in the orbitofrontal cortex by enhancing glutamatergic transmission and reducing GABAergic transmission via the 5-HT2A receptor. |
Abstract
Serotonergic psychedelics show promise in the treatment of psychiatric disorders, including obsessive-compulsive disorder. Dysfunction of the orbitofrontal cortex (OFc) has been implicated in the pathophysiology of compulsive behavior, which might be a key region for the efficacy of psychedelics. However, the effects of psychedelics on the neural activities and local excitation/inhibition (E/I) balance in the OFc are unclear. This study aimed to investigate how 25C-NBOMe, a substituted phenethylamine psychedelic, regulated the synaptic and intrinsic properties of neurons in layer II/III of the OFc. Acute brain slices containing the OFc of adult male Sprague Dawley rats were used for ex vivo whole-cell recording. The synaptic and intrinsic properties of neurons were monitored using voltage and current clamps, respectively. Electrically evoked action potential (eAP) was used to measure synaptic-driven pyramidal activity. 25C-NBOMe enhanced spontaneous neurotransmission at glutamatergic synapses but diminished that in GABAergic synapses through the 5-HT2A receptor. 25C-NBOMe also increased both evoked excitatory currents and evoked action potentials. Moreover, 25C-NBOMe promoted the excitability of pyramidal neurons but not fast-spiking neurons. Either inhibiting G protein-gated inwardly rectifying potassium channels or activating protein kinase C significantly obstructed the facilitative effect of 25C-NBOMe on the intrinsic excitability of pyramidal neurons. This work reveals the multiple roles of 25C-NBOMe in modulating synaptic and neuronal function in the OFc, which collectively promotes local E/I ratios.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 8
- Psychedelic-Induced Neural Plasticity: A Comprehensive Review and a Discussion of Clinical Implications. Brain Sciences January 25, 2025
- The effect of psilocybin on empathy and prosocial behavior: a proposed mechanism for enduring antidepressant effects. npj Mental Health Research February 20, 2024
- Single-dose psilocybin rapidly and sustainably relieves allodynia and anxiodepressive-like behaviors in mouse models of chronic pain Nature Neuroscience October 2, 2025
- Neurotoxic effects of hallucinogenic drugs 25H-NBOMe and 25H-NBOH in organotypic hippocampal cultures Heliyon June 27, 2023
- Psilocybin prevents habituation to familiar stimuli and preserves sensitivity to sound following repeated stimulation in mouse primary auditory cortex bioRxiv (Cold Spring Harbor Laboratory) September 30, 2024
and 3 more in the library
Cites 16
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future. Neuropsychopharmacology April 26, 2017
- Global Street Food: la cocina de la calle Diseño interior 2009
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- Psychiatry & the psychedelic drugs. Past, present & future. Neuropharmacology December 25, 2017
and 11 more in the library