Aripiprazole is an antipsychotic drug characterized by partial agonist activity at D2 receptors to normalize both hyperdopaminergic and hypodopaminergic states. Traditional D2 antagonist antipsychotic drugs have been shown previously to reduce dopamine neuron activity through action on D2 autoreceptors to produce an overexcitation-induced cessation of cell firing, referred to as depolarization block. It is unclear whether aripiprazole reduces dopamine neuron activity via inhibition or, as seen following D2 antagonist administration, depolarization block. The impact of acute and repeated aripiprazole treatment was examined in the methylazoxymethanol acetate (MAM) rodent model to observe its effects on a hyperdopaminergic system, compared to normal rats. We found that administration of aripiprazole acutely or after 1 or 7 days of withdrawal from 21-day repeated treatment led to a decrease in the number of spontaneously active dopamine neurons in MAM rats but not in controls. This reduction was not reversed by apomorphine (100-200 µg/kg i.p. or 20 µg/kg i.v.) administration, suggesting that it was not due to depolarization block. In contrast, 1 h after induction of depolarization block of dopamine neurons by acute haloperidol treatment (0.6 mg/kg i.p.), aripiprazole (1 mg/kg, i.p.) reversed the depolarization block state. Therefore, aripiprazole rapidly reduced the hyperdopaminergic activity selectively in MAM rats. The reduction is unlikely due to depolarization block and persists following 7-day withdrawal from repeated treatment. Aripiprazole also removes haloperidol-induced depolarization block in MAM rats, which may underlie the acute psychotic state often observed with switching to this treatment.

中文翻译：

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D2部分激动剂阿立哌唑对精神分裂症MAM神经发育模型中多巴胺神经元活性的状态依赖性影响。

阿立哌唑是一种抗精神病药，其特征在于对D2受体具有部分激动剂活性，以使高多巴胺能和低多巴胺能状态均正常化。先前已显示出传统的D2拮抗剂抗精神病药会通过作用于D2自身受体来降低多巴胺神经元的活性，从而产生过度兴奋诱导的细胞放电停止，这被称为去极化阻滞。尚不清楚阿立哌唑是否通过抑制作用降低多巴胺神经元活性，或者在给予D2拮抗剂后可见去极化阻滞。与正常大鼠相比，在乙酸甲基乙氧基甲醇酯（MAM）啮齿动物模型中检查了急性和反复使用阿立哌唑的影响，以观察其对高多巴胺能系统的影响。我们发现急性或在21天重复治疗停药1或7天后施用阿立哌唑会导致MAM大鼠中自发活跃的多巴胺神经元数量减少，但在对照组中却没有。阿扑吗啡（100-200 µg / kg ip或20 µg / kg iv）给药并不能逆转这种降低，表明这不是由于去极化阻滞所致。相反，在急性氟哌啶醇（0.6 mg / kg ip）诱导多巴胺神经元去极化阻滞后1小时，阿立哌唑（1 mg / kg，ip）逆转了去极化阻滞状态。因此，阿立哌唑迅速降低了MAM大鼠的高多巴胺能活性。由于去极化阻滞，这种减少不太可能发生，并且在退出重复治疗7天后仍然持续。