Effects of novel antipsychotics, amisulpiride and aripiprazole, on maternal behavior in rats
Effects of novel antipsychotics, amisulpiride and aripiprazole, on maternal behavior in rats
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DOI：
10.1007/s00213-005-0091-7
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发表时间：
2005-09-01
影响因子：
3.4
通讯作者：
Kapur, S
中科院分区：
文献类型：
--
作者：
Li, M;Budin, R;Kapur, S
理论基础：大鼠的母性行为，包括复杂的动机和社会因素，被目前可用的典型和非典型抗精神病药物扰乱。据认为，这种干扰反映了抗精神病药物的副作用，模拟了抗精神病药物诱导的负面或缺陷状态。阿米舒必利和阿立哌唑是一种新型的非典型抗精神病药物，其作用机制有别于目前的典型和非典型抗精神病药物。这些药物对母亲行为的影响还没有得到研究。目的：系统研究阿米苏必利和阿立哌唑对产后雌性大鼠母体行为的影响。方法：单次注射阿米苏必利(10，30,100 mg/kg，S.C.)后，在24小时内重复检测母鼠行为的各个组成部分(取仔、舔仔、筑巢和哺乳)。阿立哌唑(3、10、30 mg/kg)。结果：低剂量阿米舒必利(10 mg/kg和30 mg/kg)可促进幼崽的舔食，而最高剂量则干扰幼崽取回和筑巢等母体行为的活动成分。与其他抗精神病药物相比，其起效时间延迟、持续时间延长。阿立哌唑，即使在最高剂量(30毫克/公斤)也不会影响取回幼崽或舔幼崽。然而，它确实扰乱了筑巢，并导致了对幼崽的加强护理。结论：这两种药物的独特作用可能是由于它们在中脑边缘多巴胺突触上的独特作用。阿立哌唑减少母体行为的主要成分可能与其部分兴奋作用有关，而阿米舒利促进幼鼠舔食可能与其对突触前自身受体的剂量依赖性优先效应有关。对这些发现的潜在临床意义进行了讨论。
Rationale: Rat maternal behavior, which entails complex motivational and social factors, is disrupted by the currently available typical and atypical antipsychotics. It is thought that this disruption reflects a side effect of antipsychotics, modeling the neuroleptic-induced negative or deficit state. Amisulpiride and aripiprazole are new atypical antipsychotics with mechanisms of action distinct from the current typical and atypical antipsychotics. The effects of these drugs on maternal behavior have not been explored. Objective: In the present study, we systematically examined the behavioral effects of amisulpiride and aripiprazole on maternal behavior in postpartum female rats. Methods: Various components of maternal behavior (pup retrieval, pup licking, nest building and pup nursing) were examined repeatedly over a period of 24 h after a single injection of three doses of amisulpiride (10, 30, and 100 mg/kg s.c.) and aripiprazole (3, 10, and 30 mg/kg). Results: Amisulpiride at the lower doses (10 and 30 mg/kg) enhanced pup licking, and only at the highest dose disrupted the active components of maternal behavior such as pup retrieval and nest building. Its effect was delayed in onset and prolonged as compared to other antipsychotics. Aripiprazole, even at the highest dose (30 mg/kg) did not impair pup retrieval or pup licking. However, it did disrupt nest building and led to enhanced pup nursing. Conclusions: The unique effects of these two drugs may be due to their unique actions at the mesolimbic dopamine synapses. The sparing of the major components of maternal behavior by aripiprazole may be related to its partial agonist effects, whereas the enhancement of pup licking by amisulpiride may be related to its dose-dependent preferential effect on the presynaptic autoreceptors. The potential clinical implications of these findings are discussed.