Effect of the selective 5-HT7 receptor antagonist SB 269970 in animal models of anxiety and depression.

Neuropharmacology

Department of New Drugs Research, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, Kraków PL 31-343, Poland.

Published: September 2006

The aim of the present study was to examine the effect of the selective 5-HT7 receptor antagonist SB 269970 (0.25-20 mg/kg) in the behavioral tests commonly used for predicting anxiolytic- and antidepressant-like activity. Diazepam and imipramine were used as standard drugs. SB 269970 (in one medium dose of 0.5 or 1 mg/kg) exerted a specific antianxiety-like effect in the Vogel drinking test in rats, in the elevated plus-maze test in rats and in the four-plate test in mice. Moreover, SB 269970 (in one medium dose of 5 or 10 mg/kg) showed antidepressant-like activity in the forced swimming and the tail suspension tests in mice. At the same time, the tested compound at doses of 1-20 mg/kg did not change the spontaneous locomotor activity of mice. The potential anxiolytic and antidepressant effects produced by SB 269970 were weaker than those of the reference drugs employed. It is noteworthy that the active doses of SB 269970 were devoid of any visible motor side-effects. In conclusion, the results of our studies indicate that 5-HT7 receptor antagonists may play a role in the therapy of both anxiety and depression.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuropharm.2006.04.017DOI Listing

Publication Analysis

Top Keywords

5-ht7 receptor
12
selective 5-ht7
8
receptor antagonist
8
antagonist 269970
8
anxiety depression
8
antidepressant-like activity
8
269970 medium
8
medium dose
8
dose mg/kg
8
test rats
8

Similar Publications

Synthesis, Pharmacological Characterization, and Binding Mode Analysis of 8-Hydroxy-Tetrahydroisoquinolines as 5-HT Receptor Inverse Agonists.

ACS Chem Neurosci

January 2025

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Jagtvej 160, 2100 Copenhagen, Denmark.

The serotonin 7 receptor (5-HTR) regulates various processes in the central nervous system, including mood, learning, and circadian rhythm control, among others. Receptor activation can lead to activation of the Gα protein and a subsequent increase of intracellular cyclic adenosine monophosphate (cAMP). Receptor interaction with inverse agonists results in a decrease of basal cAMP levels and therefore a downstream effect of reduced neuronal excitability and neurotransmission.

View Article and Find Full Text PDF

The hormone and neurotransmitter serotonin regulates numerous physiological functions within the central nervous system and in the periphery upon binding to specific receptors. In the periphery, the serotonin receptor 7 (5-HT7R) is expressed on different immune cells including monocytes and macrophages. To investigate the impact of 5-HT7R-mediated signaling on macrophage properties, we used human THP-1 cells and differentiated them into pro-inflammatory M1- and anti-inflammatory M2-like macrophages.

View Article and Find Full Text PDF

Behavioral Consequences of Hippocampal 5-HT7 Receptors Blockade in Stressed Rats.

Hippocampus

January 2025

Laboratório de Neurobiologia Do Estresse e da Depressão, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.

Serotonin (5-HT) has long been involved in response to stress and its effect may be, in part, mediated by 5-HT1a and 5-HT7 receptor subtypes in different brain structures. Both pre- and post-synaptic activation of 5-HT1a receptor, respectively, in the rat median raphe nucleus (MnRN) and hippocampus, lead to adaptation to acute inescapable stressors such as restraint and forced swim. 5-HT7 receptor (5HT7r), a stimulatory G-protein coupled receptor, has also been investigated as a possible candidate for mediating stress response.

View Article and Find Full Text PDF

Background: Homo- and heteromerization of G protein-coupled receptors (GPCRs) plays an important role in the regulation of receptor functions. Recently, we demonstrated an interaction between the serotonin receptor 7 (5-HT7R), a class A GPCR, and the cell adhesion molecule CD44. However, the functional consequences of this interaction on 5-HT7R-mediated signaling remained enigmatic.

View Article and Find Full Text PDF

The first of our aims in this study was to investigate the effects of 5-HT2AR, 5-HT7R, and A2AR blockades on miR-27b-3p expression in the short and long-term in neuroblastoma cells. Our second aim was to reduce the expression of pERK and suppress proliferation by blocking the 5-HT2AR with ketanserin. Our third aim was to reduce the expression of pAKT and induce apoptosis by blocking the A2AR and 5-HT7R with MSX3 and SB269970.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!