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Chronic Treatment With Aripiprazole Prevents Development of Dopamine Supersensitivity and Potentially Supersensitivity Psychosis

Background: Long-term treatment of schizophrenia with antipsychotics is crucial for relapse prevention, but a prolonged blockade of D(2) dopamine receptors may lead to the development of supersensitivity psychosis. We investigated the chronic effects of aripiprazole (ARI) on dopamine sensitivity. Me...

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Autores principales: Tadokoro, Shigenori, Okamura, Naoe, Sekine, Yoshimoto, Kanahara, Nobuhisa, Hashimoto, Kenji, Iyo, Masaomi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446226/
https://www.ncbi.nlm.nih.gov/pubmed/21402722
http://dx.doi.org/10.1093/schbul/sbr006
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author Tadokoro, Shigenori
Okamura, Naoe
Sekine, Yoshimoto
Kanahara, Nobuhisa
Hashimoto, Kenji
Iyo, Masaomi
author_facet Tadokoro, Shigenori
Okamura, Naoe
Sekine, Yoshimoto
Kanahara, Nobuhisa
Hashimoto, Kenji
Iyo, Masaomi
author_sort Tadokoro, Shigenori
collection PubMed
description Background: Long-term treatment of schizophrenia with antipsychotics is crucial for relapse prevention, but a prolonged blockade of D(2) dopamine receptors may lead to the development of supersensitivity psychosis. We investigated the chronic effects of aripiprazole (ARI) on dopamine sensitivity. Methods: We administered ARI (1.5 mg/kg/d), haloperidol (HAL; 0.75 mg/kg/d), or vehicle (VEH) via minipump for 14 days to drug-naive rats or to rats pretreated with HAL (0.75 mg/kg/d) or VEH via minipump for 14 days. On the seventh day following treatment cessation, we examined the effects of the treatment conditions on the locomotor response to methamphetamine and on striatal D(2) receptor density (N = 4-10/condition/experiment). Results: Chronic treatment with HAL led to significant increases in locomotor response and D(2) receptor density, compared with the effects of chronic treatment with either VEH or ARI; there were no significant differences in either locomotor response or D(2) density between the VEH- and ARI-treated groups. We also investigated the effects of chronic treatment with HAL, ARI, or VEH preceded by HAL or VEH treatment on locomotor response and D(2) density. ANOVA analysis indicated that the rank ordering of groups for both locomotor response and D(2) density was HAL-HAL > HAL-VEH > HAL-ARI > VEH-VEH. Conclusions: Chronic treatment with ARI prevents development of dopamine supersensitivity and potentially supersensitivity psychosis, suggesting that by reducing excessive sensitivity to dopamine and by stabilizing sensitivity for an extended period of time, ARI may be helpful for some patients with treatment-resistant schizophrenia.
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spelling pubmed-34462262012-09-19 Chronic Treatment With Aripiprazole Prevents Development of Dopamine Supersensitivity and Potentially Supersensitivity Psychosis Tadokoro, Shigenori Okamura, Naoe Sekine, Yoshimoto Kanahara, Nobuhisa Hashimoto, Kenji Iyo, Masaomi Schizophr Bull Regular Article Background: Long-term treatment of schizophrenia with antipsychotics is crucial for relapse prevention, but a prolonged blockade of D(2) dopamine receptors may lead to the development of supersensitivity psychosis. We investigated the chronic effects of aripiprazole (ARI) on dopamine sensitivity. Methods: We administered ARI (1.5 mg/kg/d), haloperidol (HAL; 0.75 mg/kg/d), or vehicle (VEH) via minipump for 14 days to drug-naive rats or to rats pretreated with HAL (0.75 mg/kg/d) or VEH via minipump for 14 days. On the seventh day following treatment cessation, we examined the effects of the treatment conditions on the locomotor response to methamphetamine and on striatal D(2) receptor density (N = 4-10/condition/experiment). Results: Chronic treatment with HAL led to significant increases in locomotor response and D(2) receptor density, compared with the effects of chronic treatment with either VEH or ARI; there were no significant differences in either locomotor response or D(2) density between the VEH- and ARI-treated groups. We also investigated the effects of chronic treatment with HAL, ARI, or VEH preceded by HAL or VEH treatment on locomotor response and D(2) density. ANOVA analysis indicated that the rank ordering of groups for both locomotor response and D(2) density was HAL-HAL > HAL-VEH > HAL-ARI > VEH-VEH. Conclusions: Chronic treatment with ARI prevents development of dopamine supersensitivity and potentially supersensitivity psychosis, suggesting that by reducing excessive sensitivity to dopamine and by stabilizing sensitivity for an extended period of time, ARI may be helpful for some patients with treatment-resistant schizophrenia. Oxford University Press 2012-09 2011-03-14 /pmc/articles/PMC3446226/ /pubmed/21402722 http://dx.doi.org/10.1093/schbul/sbr006 Text en © The Authors 2012. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Regular Article
Tadokoro, Shigenori
Okamura, Naoe
Sekine, Yoshimoto
Kanahara, Nobuhisa
Hashimoto, Kenji
Iyo, Masaomi
Chronic Treatment With Aripiprazole Prevents Development of Dopamine Supersensitivity and Potentially Supersensitivity Psychosis
title Chronic Treatment With Aripiprazole Prevents Development of Dopamine Supersensitivity and Potentially Supersensitivity Psychosis
title_full Chronic Treatment With Aripiprazole Prevents Development of Dopamine Supersensitivity and Potentially Supersensitivity Psychosis
title_fullStr Chronic Treatment With Aripiprazole Prevents Development of Dopamine Supersensitivity and Potentially Supersensitivity Psychosis
title_full_unstemmed Chronic Treatment With Aripiprazole Prevents Development of Dopamine Supersensitivity and Potentially Supersensitivity Psychosis
title_short Chronic Treatment With Aripiprazole Prevents Development of Dopamine Supersensitivity and Potentially Supersensitivity Psychosis
title_sort chronic treatment with aripiprazole prevents development of dopamine supersensitivity and potentially supersensitivity psychosis
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446226/
https://www.ncbi.nlm.nih.gov/pubmed/21402722
http://dx.doi.org/10.1093/schbul/sbr006
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