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阻断血清素 5-HT 受体可增强多巴胺 D 激活诱导的高架十字迷宫中幼仔取回行为的破坏,但对 D 阻断诱导的破坏无影响。

Blockade of serotonin 5-HT receptors potentiates dopamine D activation-induced disruption of pup retrieval on an elevated plus maze, but has no effect on D blockade-induced one.

机构信息

Faculty of Psychology, Southwest University, Chongqing, China; Key Laboratory of Cognition and Personality, Southwest University, Ministry of Education, China.

Faculty of Psychology, Southwest University, Chongqing, China; Chongqing Collaborative Innovation Center for Brain Science, Chongqing, China; Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE 68588-0308, USA.

出版信息

Pharmacol Biochem Behav. 2018 Aug;171:74-84. doi: 10.1016/j.pbb.2018.06.004. Epub 2018 Jun 23.

DOI:10.1016/j.pbb.2018.06.004
PMID:29944910
Abstract

Appetitive aspect of rat maternal behavior, such as pup retrieval, is motivationally driven and sensitive to dopamine disturbances. Activation or blockade of dopamine D receptors causes a similar disruption of pup retrieval, which may also reflect an increase in maternal anxiety and/or a disruption of executive function. Recent work indicates that serotonin 5-HT receptors also play an important role in rat maternal behavior. Given the well-known modulation of 5-HT on the mesolimbic and mesocortical dopamine functions, the present study examined the extent to which blockade of 5-HT receptors on dopamine D-mediated maternal effects using a pup retrieval on the elevated plus maze (EPM) test. Sprague-Dawley postpartum female rats were acutely injected with quinpirole (a D agonist, 0.10 and 0.25 mg/kg, sc), or haloperidol (a D antagonist, 0.1 or 0.2 mg/kg, sc), in combination of MDL100907 (a 5-HT receptor antagonist, 1.0 mg/kg, sc, 30 min before quinpirole or haloperidol injection) or saline and tested at 30, 90 and 240 min after quinpirole or haloperidol injection on postpartum days 3 and 7. Quinpirole and haloperidol decreased the number of pup retrieved (an index of maternal motivation) and sequential retrieval score (an index of executive function), prolonged the pup retrieval latencies, reduced the percentage of time spent on the open arms (an index of maternal anxiety), and decreased the distance travelled on the maze in a dose-dependent and time-dependent fashion. MDL100907 treatment by itself had no effect on pup retrieval, but it exacerbated the quinpirole-induced disruption of pup retrieval, but had no effect on the haloperidol-induced one. These findings suggest a complex interactive effect between 5-HT and D receptors on one or several maternal processes (maternal motivation, anxiety and executive function), and support the idea that one molecular mechanism by which 5-HT receptors mediate maternal behavior is through its modulation of D receptors.

摘要

大鼠母性行为的食欲方面,例如幼崽回收,是由动机驱动的,对多巴胺紊乱敏感。多巴胺 D 受体的激活或阻断会导致幼崽回收的类似中断,这也可能反映出母鼠焦虑增加和/或执行功能中断。最近的研究表明,5-羟色胺 5-HT 受体在大鼠母性行为中也起着重要作用。鉴于 5-HT 对中脑边缘和中脑皮质多巴胺功能的显著调节作用,本研究使用高架十字迷宫(EPM)测试检查了 5-HT 受体阻断对多巴胺 D 介导的母性行为的影响程度。产后第 3 天和第 7 天,给急性注射喹吡罗(D 激动剂,0.10 和 0.25mg/kg,sc)或氟哌啶醇(D 拮抗剂,0.1 或 0.2mg/kg,sc)的 Sprague-Dawley 产后雌性大鼠联合 MDL100907(5-HT 受体拮抗剂,1.0mg/kg,sc,在喹吡罗或氟哌啶醇注射前 30 分钟)或生理盐水,并在喹吡罗或氟哌啶醇注射后 30、90 和 240 分钟进行测试。喹吡罗和氟哌啶醇降低了幼崽回收数量(母性行为动机的指标)和连续回收评分(执行功能的指标),延长了幼崽回收潜伏期,降低了在打开臂上花费的时间百分比(母性行为焦虑的指标),并减少了在迷宫上的行驶距离,呈剂量依赖性和时间依赖性。MDL100907 本身的治疗对幼崽回收没有影响,但它加剧了喹吡罗引起的幼崽回收中断,但对氟哌啶醇引起的幼崽回收没有影响。这些发现表明 5-HT 和 D 受体之间存在复杂的相互作用,这种相互作用影响了一种或几种母性行为过程(母性行为动机、焦虑和执行功能),并支持 5-HT 受体通过调节 D 受体来介导母性行为的一个分子机制的观点。

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