Sedation and disruption of maternal motivation underlie the disruptive effects of antipsychotic treatment on rat maternal behavior.
Sedation and disruption of maternal motivation underlie the disruptive effects of antipsychotic treatment on rat maternal behavior.
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DOI：
10.1016/j.pbb.2008.11.006
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发表时间：
2009-03
影响因子：
3.6
通讯作者：
Li, Ming
中科院分区：
文献类型：
--
作者：
Zhao, Changjiu;Li, Ming
关键词：
本研究探讨了抗精神病药物诱导的母亲行为缺陷的行为机制。各组产后大鼠分别于产后第4天和第6天分别给予氟哌啶醇（0.1 mg/kg）、氯氮平（10.0 mg/kg）、氯二氮平（5.0 mg/kg，一种抗焦虑药）或对照剂（0.9%生理盐水）治疗，分别在幼崽分离（实验前将幼崽与母崽分离4 h）和不与母崽分离的情况下，对其母性行为进行检测。产后第8 ~ 12天，观察产妇行为及药物镇静情况。结果表明，分离幼崽可以增加母性动机，显著缩短氯氮平延长的幼犬接近潜伏期，增加幼犬舔舐和哺乳，但不能逆转氟哌啶醇和氯氮平治疗的哺乳期大鼠找回幼犬和筑巢的缺陷。反复氟哌啶醇治疗对幼犬的恢复和筑窝的破坏逐渐增强，镇静作用减弱。相比之下，氯氮平对幼犬恢复的干扰逐渐减弱，镇静作用也随之减弱。基于这些发现，我们认为抗精神病药物至少在一定程度上通过抑制母亲的动机来破坏母亲的积极反应，药物诱导的镇静也有助于这种破坏作用，尤其是氯氮平。
The behavioral mechanisms underlying antipsychotic-induced maternal behavior deficits were examined in the present study. Different groups of postpartum rats were treated with haloperidol (0.1 mg/kg), clozapine (10.0 mg/kg), chlordiazepoxide (5.0 mg/kg, an anxiolytic) or vehicle (0.9% saline) on Days 4 and 6 postpartum and their maternal behaviors were tested under either pup-separation (e.g. pups were removed from their mothers for 4 h before testing) or no-pup-separation condition. Maternal behavior and drug-induced sedation were further tested for 3 days from Day 8 to 12 postpartum. Results show that pup-separation, which putatively increases maternal motivation, did significantly shorten clozapine-elongated pup approach latency, increase pup licking and nursing but fail to reverse the deficits in pup retrieval and nest building in the lactating rats treated with haloperidol and clozapine. Repeated haloperidol treatment produced a progressively enhanced disruption on pup retrieval and nest building and an attenuated sedation. In contrast, clozapine showed a progressively diminished disruption on pup retrieval and a concomitantly diminished sedative effect. Based on these findings, we suggest that antipsychotic drugs disrupt active maternal responses at least in part by suppressing maternal motivation, and drug-induced sedation also contributes to this disruptive effect, especially with clozapine.
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