Related Experiment Video
Updated: Mar 20, 2026
11:27
The Use of Pharmacological-challenge fMRI in Pre-clinical Research: Application to the 5-HT System
Published on: April 25, 2012
16.0K
Selective serotonin 5-HT1A receptor biased agonists elicitdistinct brain activation patterns: a pharmacoMRI study
G Becker1,2, R Bolbos3, N Costes3
1Université Claude Bernard Lyon 1, Centre de Recherche en Neurosciences de Lyon, CNRS, INSERM, Lyon, France.
Scientific Reports
|May 24, 2016
Summary
Biased serotonin 1A (5-HT1A) receptor agonists show distinct brain activity patterns compared to traditional agonists. This neuroimaging study supports biased agonism as a novel therapeutic strategy in neuropsychopharmacology.
Area of Science:
- Neuroscience
- Pharmacology
- Medical Imaging
Background:
- Serotonin 1A (5-HT1A) receptors are crucial in physiological and pathological processes, making them a key therapeutic target.
- Biased agonism is a pharmacological concept suggesting selective agonists can direct receptor signaling to specific intracellular pathways.
- This opens avenues for developing drugs that target specific receptor subtypes within distinct brain regions.
Purpose of the Study:
- To investigate the in vivo effects of different serotonin 1A (5-HT1A) receptor agonists and an antagonist on brain activity using functional magnetic resonance imaging (fMRI).
- To provide functional evidence supporting the concept of biased agonism by observing distinct brain blood oxygen level-dependent (BOLD) signal patterns.
- To explore the potential of neuroimaging techniques in understanding biased agonism for neuropsychopharmacological applications.
Main Methods:
- Utilized 7 Tesla functional magnetic resonance imaging (7T-fMRI) in anesthetized rats.
- Administered three 5-HT1A receptor agonists (8-OH-DPAT, F13714, F15599) and one antagonist (MPPF).
- Compared the influence of these compounds on the brain blood oxygen level-dependent (BOLD) signal.
Main Results:
- Observed distinct BOLD signal patterns for biased 5-HT1A receptor agonists compared to a classical agonist and a silent antagonist.
- Demonstrated for the first time contrasting brain activity profiles induced by biased agonists.
- Provided region-specific functional information on 5-HT1A receptor activation.
Conclusions:
- The study provides functional neuroimaging evidence supporting the concept of biased agonism at the 5-HT1A receptor.
- The observed contrasting BOLD signal patterns highlight the potential for developing subtype- and region-specific therapies.
- This translatable neuroimaging approach can advance the exploration of biased agonism in neuropsychopharmacology.
More Related Videos
08:49Rapid In Situ Hybridization using Oligonucleotide Probes on Paraformaldehyde-prefixed Brain of Rats with Serotonin Syndrome
Published on: September 23, 2015
9.3K
14:21Creating Dynamic Images of Short-lived Dopamine Fluctuations with lp-ntPET: Dopamine Movies of Cigarette Smoking
Published on: August 6, 2013
18.9K
Related Concept Videos
01:23Antidepressant Drugs: MAOIs and Other Agents
1.2K
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...
1.2K
01:23Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists
1.2K
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...
1.2K
01:16Adrenergic Agonists: Chemistry and Structure-Activity Relationship
4.1K
Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
4.1K
01:21Antipsychotic Drugs: Typical and Atypical Agents
1.2K
Antipsychotic drugs are classified into first-generation (typical) drugs including phenothiazines; and second-generation (atypical) drugs. Chlorpromazine hydrochloride (Thorazine), a phenothiazine derivative, broadly impacts the central, autonomic, and endocrine systems. This drug, along with typical agents like haloperidol (Haldol), primarily works by antagonizing D2 receptors, thus reducing dopaminergic neurotransmission. However, typical antipsychotics can cause side effects such as sedation...
1.2K
01:21Drugs Affecting Neurotransmitter Release or Uptake
1.8K
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...
1.8K
01:25Adrenergic Agonists: Indirect-Acting Agents
3.0K
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...
3.0K