Related Experiment Video
Updated: May 20, 2025
08:49
Rapid In Situ Hybridization using Oligonucleotide Probes on Paraformaldehyde-prefixed Brain of Rats with Serotonin Syndrome
Published on: September 23, 2015
8.8K
The Selective 5HT2A Receptor Agonist, 25CN-NBOH Exerts Excitatory and Inhibitory Cellular Actions on Mouse Medial
Yang Wang1, Jesper L Kristensen1, Kristi A Kohlmeier1
1Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Synapse (New York, N.Y.)
|March 24, 2025
Summary
Psychedelic 25CN-NBOH enhances excitatory transmission via serotonin receptors but suppresses neuron firing through M-current channels, revealing complex dual actions. This deepens understanding of psychedelic mechanisms for stress-related disorders.
Area of Science:
- Neuroscience
- Psychopharmacology
Background:
- Psychedelic compounds show therapeutic potential for stress disorders.
- Serotonergic system modulation, particularly via serotonin type 2A receptor (5-HT2AR), is a key focus.
- 25CN-NBOH is a synthetic psychedelic with high 5-HT2AR affinity and anti-anxiety effects.
Purpose of the Study:
- Investigate the electrophysiological effects of 25CN-NBOH on medial prefrontal cortex (mPFC) pyramidal neurons.
- Determine the role of 5-HT2AR and M-current channels in these effects.
Main Methods:
- Whole-cell patch clamp recordings in mouse brain slices.
- Acute and long-term exposure to 25CN-NBOH at 10 µM and 200 nM.
- Assessment of spontaneous excitatory postsynaptic currents (sEPSCs) and action potential firing rates.
- Use of M-current blocker XE-991.
Main Results:
- Acute 10 µM 25CN-NBOH increased sEPSC frequency, dependent on 5-HT2AR activation (not seen with chronic exposure or 200 nM).
- Both concentrations of 25CN-NBOH suppressed neuronal firing rate acutely and after 1 hour of exposure.
- This firing rate suppression was independent of 5-HT2AR but mediated by M-current channels.
Conclusions:
- 25CN-NBOH exhibits a dual action: enhancing excitatory transmission and reducing neuronal excitability.
- Findings elucidate cellular consequences of 5-HT2AR agonism and M-current modulation by psychedelics.
- Contributes to understanding therapeutic mechanisms of serotonergic psychedelics for stress-related disorders.
More Related Videos
Related Concept Videos
01:23Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists
199
Serotonin, a crucial neurotransmitter synthesized by enterochromaffin cells, plays a cardinal role in regulating gastrointestinal (GI) motility. With over 90% of the body's total serotonin in the GI tract, its influence on digestive processes is profound. Serotonin is swiftly released upon various stimuli, such as food boluses or certain drugs, triggering intrinsic sensory neurons in the myenteric plexus and extrinsic vagal and spinal sensory neurons. This leads to the activation of the...
199
01:25Dose-Response Relationship: Selectivity and Specificity
6.3K
Drugs exert their therapeutic effects by interacting with receptors, enzymes, or ion channels that are present throughout the human body. The strength and duration of the interaction between a drug and its target receptor are characterized by the selectivity and specificity of the drug. Selectivity refers to a drug's strong preference for its intended target over other targets. For instance, isoprenaline, a non-selective β-adrenergic agonist, interacts with both β1- and...
6.3K
01:21Drugs Affecting Neurotransmitter Release or Uptake
911
Certain drugs can affect how neurotransmitters called catecholamines, are released or taken back up in the adrenergic neuron. They can have different effects on the body's sympathetic transmission. Reserpine, a natural compound found in the Rauwolfia shrub, blocks a transporter called vesicular monoamine transporter (VMAT), which leads to a buildup of catecholamines in the cell and reduces sympathetic transmission. Another drug called guanethidine works in multiple ways, including blocking...
911
01:23Antidepressant Drugs: MAOIs and Other Agents
173
Atypical antidepressants, including bupropion (Wellbutrin), mirtazapine (Remeron), nefazodone (Serzone), trazodone (Desyrel), and vilazodone (Viibryd), offer unique mechanisms of action. Bupropion weakly inhibits dopamine and norepinephrine reuptake, aiding depression treatment and smoking cessation, with a low risk of sexual dysfunction. Mirtazapine enhances serotonin and norepinephrine neurotransmission, leading to sedation, increased appetite, and weight gain. As a result, it helps treat...
173
01:25Adrenergic Agonists: Indirect-Acting Agents
1.4K
Indirect-acting adrenergic agonists potentiate the effects of endogenous catecholamines through different mechanisms without directly binding to adrenoceptors.
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral...
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral...
1.4K
01:30Adrenergic Agonists: Direct-Acting Agents
1.3K
Drugs that mimic the action of endogenous catecholamines like noradrenaline and adrenaline are called adrenergic agonists or sympathomimetics. Based on their mechanism of action, sympathomimetics can be classified as direct-, indirect-, or mixed-acting sympathomimetics. Direct-acting adrenergic agonists activate adrenoceptors without affecting presynaptic neurons, making them independent of neuronal catecholamine-depleting agents like reserpine and guanethidine.
These agents can be classified...
These agents can be classified...
1.3K