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Co-administration of 5-HT6 receptor antagonists with clozapine, risperidone, and a 5-HT2A receptor antagonist: effects on prepulse inhibition in rats

RATIONALE: Some novel antipsychotics manifest antagonistic activity at serotonin-6 receptors; however, little is known about the role of 5-HT6 receptors in ameliorating sensory gating deficits. OBJECTIVE: We evaluated the effects of the combined administration of the 5-HT6 receptor antagonist SB 271...

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Autores principales: Fijał, Katarzyna, Popik, Piotr, Nikiforuk, Agnieszka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3889519/
https://www.ncbi.nlm.nih.gov/pubmed/23954911
http://dx.doi.org/10.1007/s00213-013-3234-2
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author Fijał, Katarzyna
Popik, Piotr
Nikiforuk, Agnieszka
author_facet Fijał, Katarzyna
Popik, Piotr
Nikiforuk, Agnieszka
author_sort Fijał, Katarzyna
collection PubMed
description RATIONALE: Some novel antipsychotics manifest antagonistic activity at serotonin-6 receptors; however, little is known about the role of 5-HT6 receptors in ameliorating sensory gating deficits. OBJECTIVE: We evaluated the effects of the combined administration of the 5-HT6 receptor antagonist SB 271046 with clozapine and haloperidol, as well as the co-administration of SB 271046 or SB 399885 with risperidone and the 5-HT2A antagonist M100907, to overcome the deficits induced by MK-801 in the prepulse inhibition (PPI) test. RESULTS: MK-801 (0.1 mg/kg) produced reliable PPI deficits. Administration of SB 271046 (6 and 9 mg/kg), SB 399885 (3 and 6 mg/kg), clozapine (2.5 mg/kg), haloperidol (0.1 and 0.2 mg/kg), risperidone (0.25–1 mg/kg), and M100907 (0.5 and 1 mg/kg) did not affect the MK-801-induced deficits, but the administration of clozapine (5 mg/kg) did reverse the effects of MK-801. In MK-801-treated rats, the co-administration of inactive doses of clozapine (2.5 mg/kg) and SB 271046 (6 mg/kg) reversed the PPI impairments compared to animals that were administered inactive doses of either clozapine or SB 271046 alone. Co-administration of risperidone (1 mg/kg) or M100907 (0.5 mg/kg) with SB 271046 (6 mg/kg) or SB 399885 (3 mg/kg) also attenuated the MK-801-induced PPI deficits. In contrast, joint administration of haloperidol and SB 271046 had no effect on the PPI deficit. CONCLUSION: The present results suggest that the 5-HT6 receptors may play adjunctive roles in antipsychotic drug action, and that the combination of 5-HT2A and 5-HT6 antagonism may represent an important element in the pharmacological profile of antipsychotic drugs.
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spelling pubmed-38895192014-01-14 Co-administration of 5-HT6 receptor antagonists with clozapine, risperidone, and a 5-HT2A receptor antagonist: effects on prepulse inhibition in rats Fijał, Katarzyna Popik, Piotr Nikiforuk, Agnieszka Psychopharmacology (Berl) Original Investigation RATIONALE: Some novel antipsychotics manifest antagonistic activity at serotonin-6 receptors; however, little is known about the role of 5-HT6 receptors in ameliorating sensory gating deficits. OBJECTIVE: We evaluated the effects of the combined administration of the 5-HT6 receptor antagonist SB 271046 with clozapine and haloperidol, as well as the co-administration of SB 271046 or SB 399885 with risperidone and the 5-HT2A antagonist M100907, to overcome the deficits induced by MK-801 in the prepulse inhibition (PPI) test. RESULTS: MK-801 (0.1 mg/kg) produced reliable PPI deficits. Administration of SB 271046 (6 and 9 mg/kg), SB 399885 (3 and 6 mg/kg), clozapine (2.5 mg/kg), haloperidol (0.1 and 0.2 mg/kg), risperidone (0.25–1 mg/kg), and M100907 (0.5 and 1 mg/kg) did not affect the MK-801-induced deficits, but the administration of clozapine (5 mg/kg) did reverse the effects of MK-801. In MK-801-treated rats, the co-administration of inactive doses of clozapine (2.5 mg/kg) and SB 271046 (6 mg/kg) reversed the PPI impairments compared to animals that were administered inactive doses of either clozapine or SB 271046 alone. Co-administration of risperidone (1 mg/kg) or M100907 (0.5 mg/kg) with SB 271046 (6 mg/kg) or SB 399885 (3 mg/kg) also attenuated the MK-801-induced PPI deficits. In contrast, joint administration of haloperidol and SB 271046 had no effect on the PPI deficit. CONCLUSION: The present results suggest that the 5-HT6 receptors may play adjunctive roles in antipsychotic drug action, and that the combination of 5-HT2A and 5-HT6 antagonism may represent an important element in the pharmacological profile of antipsychotic drugs. Springer Berlin Heidelberg 2013-08-18 2014 /pmc/articles/PMC3889519/ /pubmed/23954911 http://dx.doi.org/10.1007/s00213-013-3234-2 Text en © The Author(s) 2013 https://creativecommons.org/licenses/by-nc/2.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Original Investigation
Fijał, Katarzyna
Popik, Piotr
Nikiforuk, Agnieszka
Co-administration of 5-HT6 receptor antagonists with clozapine, risperidone, and a 5-HT2A receptor antagonist: effects on prepulse inhibition in rats
title Co-administration of 5-HT6 receptor antagonists with clozapine, risperidone, and a 5-HT2A receptor antagonist: effects on prepulse inhibition in rats
title_full Co-administration of 5-HT6 receptor antagonists with clozapine, risperidone, and a 5-HT2A receptor antagonist: effects on prepulse inhibition in rats
title_fullStr Co-administration of 5-HT6 receptor antagonists with clozapine, risperidone, and a 5-HT2A receptor antagonist: effects on prepulse inhibition in rats
title_full_unstemmed Co-administration of 5-HT6 receptor antagonists with clozapine, risperidone, and a 5-HT2A receptor antagonist: effects on prepulse inhibition in rats
title_short Co-administration of 5-HT6 receptor antagonists with clozapine, risperidone, and a 5-HT2A receptor antagonist: effects on prepulse inhibition in rats
title_sort co-administration of 5-ht6 receptor antagonists with clozapine, risperidone, and a 5-ht2a receptor antagonist: effects on prepulse inhibition in rats
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3889519/
https://www.ncbi.nlm.nih.gov/pubmed/23954911
http://dx.doi.org/10.1007/s00213-013-3234-2
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