Maternal rat preferences for pups versus cocaine

母鼠对幼崽和可卡因的偏好

基本信息

批准号：
6862691
负责人：
Joan Irene Morrell
金额：
$ 15.55万
依托单位：
RUTGERS THE STATE UNIV OF NJ NEWARK
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-03-25 至 2008-02-29
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): In rats the reward state of the female is unique immediately postpartum; she chooses pups over cocaine. We seek to determine if the neuroendocrine basis of this unique reward state has a biological grounding in which motivation for drug reward is less, and therefore of particular interest for the human condition. We also seek to understand the neural substrate on which the neuroendocrine factors act to alter the reward state of the early postpartum female rat. We use a place preference paradigm that trains the rats to associate particular environmental cues with two unconditioned stimuli, pups and cocaine, and then tests their preference. We will expand this paradigm by systematically testing two variables, the strength of the drug stimulus, and the age of the pup stimulus (Aim 1). We hypothesize that the neuroendocrine status of the female is the basis for the genesis of the unique reward state of the early postpartum period. In Aim 2, we will test this by applying well-established models of maternal behavior that vary the basis of the behavior. We will (1) use pup-induced maternal behavior in virgin female rats to determine whether maternal status alone (the behavioral state) is sufficient to generate the specialized reward state. Then we will (2) add estrogen, (3) determine whether the hormones of pregnancy alone, in the absence of the hormones and experience of parturition and the postpartum period (maternal pregnant rat hysterectomized-ovariectomized on day 20 of pregnancy), are sufficient, and (4) determine when and if the specialized reward state occurs in pregnancy. In Aim 3, we will use this unique behavioral model to examine the neural substrate of these reward processes. The neural substrate that is engaged during this specialized reward state of the female will be identified using immunocytochemistry for three dependent variables, c-Fos to determine general engagement/activation of neurons, Homer 1a to identify glutamatergic-related activation, and CART peptide to determine pharmacologic aspects of the activation.

描述（由申请人提供）：在大鼠中，雌性的奖励状态在产后立即是独特的；她选择小狗而不是可卡因。我们试图确定这种独特奖励状态的神经内分泌基础是否具有生物学基础，其中药物奖励的动机较少，因此对人类状况特别感兴趣。我们还试图了解神经内分泌因子作用于改变产后早期雌性大鼠的奖赏状态的神经基质。我们使用位置偏好范例来训练老鼠将特定的环境线索与两种无条件刺激（幼崽和可卡因）联系起来，然后测试它们的偏好。我们将通过系统地测试两个变量来扩展这一范式，即药物刺激的强度和幼崽刺激的年龄（目标 1）。我们假设女性的神经内分泌状态是产后早期独特奖赏状态起源的基础。在目标 2 中，我们将通过应用已建立的母亲行为模型来测试这一点，这些模型会改变行为的基础。我们将（1）使用幼崽诱导的处女雌性大鼠的母性行为来确定母性状态（行为状态）是否足以产生专门的奖励状态。然后我们将（2）添加雌激素，（3）在没有激素和分娩经验以及产后期（怀孕第20天进行子宫切除-卵巢切除的母体怀孕大鼠）的情况下，确定仅妊娠激素是否足够，以及（4）确定怀孕期间何时以及是否发生特殊奖励状态。在目标 3 中，我们将使用这种独特的行为模型来检查这些奖励过程的神经基础。在女性的这种特殊奖励状态期间参与的神经底物将使用免疫细胞化学来识别三个因变量，c-Fos 来确定神经元的一般参与/激活，Homer 1a 来识别谷氨酸能相关的激活，CART 肽来确定激活的药理学方面。