Preclinical evidence for the role of serotonin receptor-subtypes in depression

1992 ◽  
Vol 4 (2) ◽  
pp. 40-45
Author(s):  
B. Olivier ◽  
J. Schipper ◽  
J.A.M. van der Heyden ◽  
A. van Hest ◽  
J. Mos ◽  
...  
Keyword(s):  
Animal Models ◽  
Clinical Research ◽  
Serotonin Receptor ◽  
Antidepressant Effect ◽  
Receptor Subtypes ◽  
Research Support ◽  
Receptor Agonists ◽  
Animal Models Of Depression ◽  
Literature Evidence

SummarySerotonin (5-HT) plays an important role in depression and specific 5-HT reuptake blockers appear to be clinically important antidepressants. It is unclear however, which serotonergic mechanism is involved in the antidepressant effect, certainly when regarding the existence of at least seven 5-HT receptor subtypes. By testing different 5-HT ligands in two animal models of depression (forced swimming and DRL72-S test) and comparison with data from literature, evidence is provided for potential antidepressant qualities of 5-HT1A receptor-agonists and 5-HT1C receptor-antagonists. Compounds binding to 5-HT1B, 5-HT2 and 5-HT3 receptors do not have an antidepressant profile. Results of clinical research support the predicted antidepressive effects of 5-HT1A receptor-agonists.

scholarly journals Elevated Brain Fatty Acid Amide Hydrolase Induces Depressive-Like Phenotypes in Rodent Models: A Review

2021 ◽  
Vol 22 (3) ◽  
pp. 1047
Author(s):  
Dorsa Rafiei ◽  
Nathan J. Kolla
Keyword(s):  
Depressive Symptoms ◽  
Fatty Acid ◽  
Animal Models ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Animal Models Of Depression ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Altered activity of fatty acid amide hydrolase (FAAH), an enzyme of the endocannabinoid system, has been implicated in several neuropsychiatric disorders, including major depressive disorder (MDD). It is speculated that increased brain FAAH expression is correlated with increased depressive symptoms. The aim of this scoping review was to establish the role of FAAH expression in animal models of depression to determine the translational potential of targeting FAAH in clinical studies. A literature search employing multiple databases was performed; all original articles that assessed FAAH expression in animal models of depression were considered. Of the 216 articles that were screened for eligibility, 24 articles met inclusion criteria and were included in this review. Three key findings emerged: (1) FAAH expression is significantly increased in depressive-like phenotypes; (2) genetic knockout or pharmacological inhibition of FAAH effectively reduces depressive-like behavior, with a dose-dependent effect; and (3) differences in FAAH expression in depressive-like phenotypes were largely localized to animal prefrontal cortex, hippocampus and striatum. We conclude, based on the animal literature, that a positive relationship can be established between brain FAAH level and expression of depressive symptoms. In summary, we suggest that FAAH is a tractable target for developing novel pharmacotherapies for MDD.

scholarly journals Progesterone after Estradiol Modulates Shuttle-Cage Escape by Facilitating Volition

2015 ◽  
Vol 9s1 ◽  
pp. JEN.S32735
Author(s):  
Darryl J. Mayeaux ◽  
Sarah M. Tandle ◽  
Sean M. Cilano ◽  
Matthew J. Fitzharris
Keyword(s):  
Depressive Symptoms ◽  
Animal Models ◽  
Electric Shock ◽  
Ovarian Hormones ◽  
Learning Task ◽  
The Other ◽  
Female Rats ◽  
Animal Models Of Depression ◽  
Escape Learning

In animal models of depression, depression is defined as performance on a learning task. That task is typically escaping a mild electric shock in a shuttle cage by moving from one side of the cage to the other. Ovarian hormones influence learning in other kinds of tasks, and these hormones are associated with depressive symptoms in humans. The role of these hormones in shuttle-cage escape learning, however, is less clear. This study manipulated estradiol and progesterone in ovariectomized female rats to examine their performance in shuttle-cage escape learning without intentionally inducing a depressive-like state. Progesterone, not estradiol, within four hours of testing affected latencies to escape. The improvement produced by progesterone was in the decision to act, not in the speed of learning or speed of escaping. This parallels depression in humans in that depressed people are slower in volition, in their decisions to take action.

scholarly journals Studies on the role of serotonin receptor subtypes in the effect of sibutramine in various feeding paradigms in rats

1999 ◽  
Vol 127 (5) ◽  
pp. 1190-1194 ◽  
Author(s):  
G Grignaschi ◽  
E Fanelli ◽  
I Scagnol ◽  
R Samanin
Keyword(s):  
Serotonin Receptor ◽  
Receptor Subtypes

scholarly journals Contribution of serotonin receptor subtypes to hallucinogenic activity of 25I-NBOMe and to its effect on neurotransmission

2020 ◽  
Vol 72 (6) ◽  
pp. 1593-1603
Author(s):  
Monika Herian ◽  
Adam Wojtas ◽  
Małgorzata Katarzyna Sobocińska ◽  
Mateusz Skawski ◽  
Alejandro González-Marín ◽  
...  
Keyword(s):  
Frontal Cortex ◽  
Serotonin Receptor ◽  
Glutamate Release ◽  
Local Administration ◽  
Receptor Subtypes ◽  
Microdialysis Probe ◽  
Selective Antagonists ◽  
Freely Moving ◽  
Rat Frontal Cortex

Abstract Background 4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) is a potent serotonin (5-HT) receptor agonist with hallucinogenic properties. The aim of our research was to examine the role of the 5-HT2A, 5-HT2C and 5-HT1A serotonin receptor subtypes in 25I-NBOMe hallucinogenic activity and its effect on dopamine (DA), 5-HT and glutamate release in the rat frontal cortex. Methods Hallucinogenic activity was investigated using the wet dog shake (WDS) test. The release of DA, 5-HT and glutamate in the rat frontal cortex was studied using a microdialysis in freely moving rats. Neurotransmitter levels were analyzed by HPLC with electrochemical detection. The selective antagonists of the 5-HT2A, 5-HT2C and 5-HT1A serotonin receptor subtypes: M100907, SB242084 and WAY100635, respectively were applied through a microdialysis probe. Results The WDS response to 25I-NBOMe (1 and 3 mg/kg) was significantly reduced by local administration of M100907 and SB242084 (100 nM). The 25I-NBOMe-induced increase in glutamate, DA and 5-HT release was inhibited by M100907 and SB242084. WAY100635 had no effect on 25I-NBOMe-induced WDS and glutamate release, while it decreased DA and 5-HT release from cortical neuronal terminals. Conclusion The obtained results suggest that 5-HT2A and 5-HT2C receptors play a role in 25I-NBOMe-induced hallucinogenic activity and in glutamate, DA and 5-HT release in the rat frontal cortex as their respective antagonists attenuated the effect of this hallucinogen. The disinhibition of GABA cells by the 5-HT1A receptor antagonist seems to underlie the mechanism of decreased DA and 5-HT release from neuronal terminals in the frontal cortex.

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