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Effect of 5-HT(6) Receptor Ligands Combined with Haloperidol or Risperidone on Antidepressant-/Anxiolytic-Like Behavior and BDNF Regulation in Hippocampus and Prefrontal Cortex of Rats
BACKGROUND: The presence of depressive and anxiety symptoms in patients with schizophrenia may have an important impact on treatment and compliance. Hence, interventions addressing such comorbidity in schizophrenia should be explored. One target may be a serotonergic 5-HT(6) receptor (5-HT(6)R) sinc...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240864/ https://www.ncbi.nlm.nih.gov/pubmed/34211274 http://dx.doi.org/10.2147/NDT.S309818 |
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author | Wesołowska, Anna Rychtyk, Joanna Gdula-Argasińska, Joanna Górecka, Katarzyna Wilczyńska-Zawal, Natalia Jastrzębska-Więsek, Magdalena Partyka, Anna |
author_facet | Wesołowska, Anna Rychtyk, Joanna Gdula-Argasińska, Joanna Górecka, Katarzyna Wilczyńska-Zawal, Natalia Jastrzębska-Więsek, Magdalena Partyka, Anna |
author_sort | Wesołowska, Anna |
collection | PubMed |
description | BACKGROUND: The presence of depressive and anxiety symptoms in patients with schizophrenia may have an important impact on treatment and compliance. Hence, interventions addressing such comorbidity in schizophrenia should be explored. One target may be a serotonergic 5-HT(6) receptor (5-HT(6)R) since its ligands displayed antidepressant- and anxiolytic-like activities in preclinical experiments. METHODS: Acute and chronic (21 days) administration of haloperidol or risperidone in combination with a selective 5-HT(6)R agonist (WAY-181187) or antagonist (SB-742457) to rats was performed for detecting antidepressant- and anxiolytic-like behaviors. In addition, the level of brain-derived neurotrophic factor (BDNF) protein and its gene expression in hippocampus and prefrontal cortex were determined. RESULTS: Both single and chronic administration of WAY-181187 with haloperidol produced antidepressant- and anxiolytic-like activities. SB-742457 did not provide full benefits in terms of improvement of haloperidol-induced adverse mood effects. However, the administration of SB-742457 with risperidone triggered its anxiolytic-like activity. Both 5-HT(6)R ligands evoked no changes in haloperidol-induced effects on BDNF level. WAY-181187 induced repression of the BDNF gene while SB-742457 increased its expression in both structures. 5-HT(6)R ligands, when combined with risperidone, did not change BDNF protein level and increased gene expression in the hippocampus, while they elevated BDNF level and potentiated gene expression in the prefrontal cortex. CONCLUSION: The combined administration of WAY-181187 and haloperidol provided the greatest benefits, which were manifested by antidepressant-like effects and suppression of the anxiogenic-like properties. The combined administration of risperidone with both agonist and antagonist resulted only in an anxiolytic-like effect. It seems that the anxiolytic-like effects induced by haloperidol or risperidone with the addition of 5-HT(6)R ligands are task-specific. The data on BDNF protein and gene expression did not fully correspond with the behavioral outcomes, and thus it appears that other factors/mechanisms are involved in the observed antidepressant- and/or anxiolytic-like effects. |
format | Online Article Text |
id | pubmed-8240864 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-82408642021-06-30 Effect of 5-HT(6) Receptor Ligands Combined with Haloperidol or Risperidone on Antidepressant-/Anxiolytic-Like Behavior and BDNF Regulation in Hippocampus and Prefrontal Cortex of Rats Wesołowska, Anna Rychtyk, Joanna Gdula-Argasińska, Joanna Górecka, Katarzyna Wilczyńska-Zawal, Natalia Jastrzębska-Więsek, Magdalena Partyka, Anna Neuropsychiatr Dis Treat Original Research BACKGROUND: The presence of depressive and anxiety symptoms in patients with schizophrenia may have an important impact on treatment and compliance. Hence, interventions addressing such comorbidity in schizophrenia should be explored. One target may be a serotonergic 5-HT(6) receptor (5-HT(6)R) since its ligands displayed antidepressant- and anxiolytic-like activities in preclinical experiments. METHODS: Acute and chronic (21 days) administration of haloperidol or risperidone in combination with a selective 5-HT(6)R agonist (WAY-181187) or antagonist (SB-742457) to rats was performed for detecting antidepressant- and anxiolytic-like behaviors. In addition, the level of brain-derived neurotrophic factor (BDNF) protein and its gene expression in hippocampus and prefrontal cortex were determined. RESULTS: Both single and chronic administration of WAY-181187 with haloperidol produced antidepressant- and anxiolytic-like activities. SB-742457 did not provide full benefits in terms of improvement of haloperidol-induced adverse mood effects. However, the administration of SB-742457 with risperidone triggered its anxiolytic-like activity. Both 5-HT(6)R ligands evoked no changes in haloperidol-induced effects on BDNF level. WAY-181187 induced repression of the BDNF gene while SB-742457 increased its expression in both structures. 5-HT(6)R ligands, when combined with risperidone, did not change BDNF protein level and increased gene expression in the hippocampus, while they elevated BDNF level and potentiated gene expression in the prefrontal cortex. CONCLUSION: The combined administration of WAY-181187 and haloperidol provided the greatest benefits, which were manifested by antidepressant-like effects and suppression of the anxiogenic-like properties. The combined administration of risperidone with both agonist and antagonist resulted only in an anxiolytic-like effect. It seems that the anxiolytic-like effects induced by haloperidol or risperidone with the addition of 5-HT(6)R ligands are task-specific. The data on BDNF protein and gene expression did not fully correspond with the behavioral outcomes, and thus it appears that other factors/mechanisms are involved in the observed antidepressant- and/or anxiolytic-like effects. Dove 2021-06-25 /pmc/articles/PMC8240864/ /pubmed/34211274 http://dx.doi.org/10.2147/NDT.S309818 Text en © 2021 Wesołowska et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Wesołowska, Anna Rychtyk, Joanna Gdula-Argasińska, Joanna Górecka, Katarzyna Wilczyńska-Zawal, Natalia Jastrzębska-Więsek, Magdalena Partyka, Anna Effect of 5-HT(6) Receptor Ligands Combined with Haloperidol or Risperidone on Antidepressant-/Anxiolytic-Like Behavior and BDNF Regulation in Hippocampus and Prefrontal Cortex of Rats |
title | Effect of 5-HT(6) Receptor Ligands Combined with Haloperidol or Risperidone on Antidepressant-/Anxiolytic-Like Behavior and BDNF Regulation in Hippocampus and Prefrontal Cortex of Rats |
title_full | Effect of 5-HT(6) Receptor Ligands Combined with Haloperidol or Risperidone on Antidepressant-/Anxiolytic-Like Behavior and BDNF Regulation in Hippocampus and Prefrontal Cortex of Rats |
title_fullStr | Effect of 5-HT(6) Receptor Ligands Combined with Haloperidol or Risperidone on Antidepressant-/Anxiolytic-Like Behavior and BDNF Regulation in Hippocampus and Prefrontal Cortex of Rats |
title_full_unstemmed | Effect of 5-HT(6) Receptor Ligands Combined with Haloperidol or Risperidone on Antidepressant-/Anxiolytic-Like Behavior and BDNF Regulation in Hippocampus and Prefrontal Cortex of Rats |
title_short | Effect of 5-HT(6) Receptor Ligands Combined with Haloperidol or Risperidone on Antidepressant-/Anxiolytic-Like Behavior and BDNF Regulation in Hippocampus and Prefrontal Cortex of Rats |
title_sort | effect of 5-ht(6) receptor ligands combined with haloperidol or risperidone on antidepressant-/anxiolytic-like behavior and bdnf regulation in hippocampus and prefrontal cortex of rats |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240864/ https://www.ncbi.nlm.nih.gov/pubmed/34211274 http://dx.doi.org/10.2147/NDT.S309818 |
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