Chronic treatment with aripiprazole prevents development of dopamine supersensitivity and potentially supersensitivity psychosis.
Chronic treatment with aripiprazole prevents development of dopamine supersensitivity and potentially supersensitivity psychosis.
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DOI：
10.1093/schbul/sbr006
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发表时间：
2012-09
影响因子：
6.6
通讯作者：
Iyo M
中科院分区：
文献类型：
--
作者：
Tadokoro S;Okamura N;Sekine Y;Kanahara N;Hashimoto K;Iyo M
背景资料：抗精神病药物对精神分裂症的长期治疗对于预防复发至关重要，但D2多巴胺受体的长期阻断可能导致超敏性精神病的发展。我们研究了阿立哌唑（ARI）对多巴胺敏感性的慢性影响。研究方法：我们通过微型泵对未用药大鼠或通过微型泵对用HAL（0.75 mg/kg/d）或VEH预处理的大鼠给予ARI（1.5 mg/kg/d）、氟哌啶醇（HAL; 0.75 mg/kg/d）或溶媒（VEH）14天。在治疗停止后的第七天，我们检查了治疗条件对甲基苯丙胺的运动反应和对纹状体D2受体密度的影响（N = 4-10/条件/实验）。结果如下：与用VEH或ARI长期治疗的效果相比，用HAL长期治疗导致运动反应和D2受体密度显著增加;在VEH和ARI治疗组之间运动反应或D2密度没有显著差异。我们还研究了在HAL或VEH治疗之前用HAL、ARI或VEH慢性治疗对运动反应和D2密度的影响。方差分析表明，运动反应和D2密度的组排序为HAL-HAL > HAL-VEH > HAL-ARI > VEH-VEH。结论：ARI的长期治疗可以预防多巴胺超敏反应和潜在的超敏反应性精神病的发展，这表明通过降低对多巴胺的过度敏感性并在较长时间内稳定敏感性，ARI可能对某些难治性精神分裂症患者有帮助。
Background: Long-term treatment of schizophrenia with antipsychotics is crucial for relapse prevention, but a prolonged blockade of D2 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 D2 receptor density (N = 4-10/condition/experiment). Results: Chronic treatment with HAL led to significant increases in locomotor response and D2 receptor density, compared with the effects of chronic treatment with either VEH or ARI; there were no significant differences in either locomotor response or D2 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 D2 density. ANOVA analysis indicated that the rank ordering of groups for both locomotor response and D2 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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影响因子：
7.6
作者：
Shapiro, DA;Renock, S;Mailman, R
通讯作者：
Mailman, R
影响因子：
64.8
作者：
MURUGAIAH, K;THEODOROU, A;MARSDEN, CD
通讯作者：
MARSDEN, CD
DOI：
10.1016/j.jchromb.2005.03.024
发表时间：
2005-07-05
影响因子：
3
作者：
Shimokawa, Y;Akiyama, H;Miyamoto, G
通讯作者：
Miyamoto, G
影响因子：
4.7
作者：
Tsai, SJ
通讯作者：
Tsai, SJ
影响因子：
5
作者：
SASAKI, H;HASHIMOTO, K;IYO, M
通讯作者：
IYO, M