BACKGROUND Evidence suggests that aripiprazole, a partial dopamine D2 and serotonin 5-HT1A receptor agonist and 5-HT2A receptor antagonist, show significant efficacy in reducing alcohol use. We have previously demonstrated that treatment with aripiprazole blocked the reinstatement of cocaine-induced behavioral sensitization in a context-dependent manner, suggesting that the treatment environment may modulate the therapeutic effects of aripiprazole. The present study aimed to evaluate the effects of treatment with aripiprazole on ethanol-induced behavioral sensitization and conditioned place preference in female mice, and the role of the treatment environment in those effects. METHODS Adult female mice were either sensitized with ethanol injections in the open-field apparatus, or conditioned with ethanol in the conditioned place preference (CPP) apparatus. Animals were then treated with vehicle or 0.1 mg/kg aripiprazole paired to the test environment (open-field or CPP apparatus) or not (home-cage treatments) for 4 alternate days, and the subsequent expression of behavioral sensitization or CPP to ethanol was evaluated during or following an ethanol re-exposure, respectively. RESULTS Repeated treatment with aripiprazole attenuated the expression of ethanol-induced behavioral sensitization regardless of the treatment environment. Treatment with aripiprazole was only effective at preventing the reinstatement of ethanol-induced CPP when paired with the ethanol-associated environment, but not when administered in the home-cage. CONCLUSIONS The present findings corroborate previous studies suggesting the effectiveness of aripiprazole for the treatment of alcohol use disorder. Our results also point to an important role of the treatment environment in the therapeutic effects of aripiprazole in rodent models of ethanol abuse.

中文翻译：

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治疗环境在阿立哌唑对乙醇诱导的行为敏化和雌性小鼠条件性位置偏爱的影响中的作用。

背景技术证据表明，阿立哌唑，部分多巴胺D2和5-羟色胺5-HT1A受体激动剂和5-HT2A受体拮抗剂显示出显着的减少酒精使用的功效。我们以前已经证明用阿立哌唑治疗以上下文依赖的方式阻止了可卡因诱导的行为敏化的恢复，这表明治疗环境可能会调节阿立哌唑的治疗效果。本研究旨在评估阿立哌唑对雌性小鼠乙醇诱导的行为敏化和条件性位置偏爱的影响，以及治疗环境在这些影响中的作用。方法成年雌性小鼠在开放视野仪器中用乙醇注射致敏，或在条件放置偏好（CPP）设备中用乙醇进行条件调整。然后将动物与赋形剂或0.1 mg / kg的阿立哌唑配对或不配对（在野外或CPP装置中）测试环境（家庭笼治疗），每隔4天处理一次，随后对乙醇的行为敏化或CPP表达为在乙醇再暴露期间或之后分别进行评估。结果无论治疗环境如何，阿立哌唑的反复治疗均减弱了乙醇诱导的行为敏化的表达。当与乙醇相关的环境配对时，用阿立哌唑治疗仅能有效地阻止乙醇诱导的CPP的恢复，但在家庭笼中给药时则无效。结论本研究结果证实了先前的研究，表明阿立哌唑治疗酒精使用障碍的有效性。我们的研究结果还指出，在乙醇滥用的啮齿动物模型中，治疗环境在阿立哌唑的治疗作用中具有重要作用。