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Title: Characteristics of functional selectivity new 5-HT1A serotonin receptor agonists

Author:

Głuch-Lutwin, Monika

Date:

Type:

Praca doktorska

Abstract:

The first part of the dissertation describes in vitro studies of the functional profile for new selective 5-HT1A receptor ligands. For the first time, they included the parallel characterization of several dozen 5-HT1A receptor ligands in several signaling pathways (cAMP inhibition, ERK1/2 phosphorylation, Ca2+ mobilization, β-arrestin recruitment), which resulted in a pioneering discovery of numerous and diverse functional profiles. Ligands with higher than before functional selectivity for ERK1/2 phosphorylation have been described, as well as for the first time ligands with a clear preference for β-arrestin recruitment. In vivo studies investigated the potential antidepressant properties of four selected 5-HT1A receptor biased agonists, both in the basic forced swimming test in mice and, for the first time, for such ligands, in murine models of corticosterone-induced depression and unpredictable chronic mild stress. The tested compounds showed significant activity after a single administration, which distinguishes them from the currently available antidepressants, and the behavioral effects were correlated with favorable changes in the level of pERK1/2 in the frontal cortex and hippocampus. The impact of the tested compounds on the consolidation process of memory traces in the novel object recognition test was also assessed.

Place of publishing:

Level of degree:

2 - studia doktoranckie

Degree discipline:

Degree grantor:

Rada Dyscypliny Nauki farmaceutyczne

Promoter:

Kołaczkowski, Marcin ; Pytka, Karolina

Date issued:

Identifier:

oai:dl.cm-uj.krakow.pl:4960

Call number:

Language:

Access rights:

tylko w bibliotece

Subject and keywords:

functional selectivity 5-HT1A serotonin receptor 5-HT1A agonists depression

Object collections:

Digital Medical Library > PhD thesis database

Last modified:

Mar 22, 2024

In our library since:

Mar 2, 2023

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0

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All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/4961

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Edition name	Date
ZB-136385	Mar 22, 2024

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