Maternal rat preferences for pups versus cocaine

描述(申请人提供)：在老鼠身上，雌性老鼠产后的奖赏状态是独一无二的；她选择幼崽而不是可卡因。我们试图确定这种独特的奖赏状态的神经内分泌基础是否有生物学基础，即药物奖赏的动机较少，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其改变产后早期雌性大鼠奖赏状态的神经底物。我们使用地点偏好范式，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，这两个变量是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形成的基础。在目标2中，我们将通过应用成熟的母性行为模型来测试这一点，这些模型改变了行为的基础。我们将(1)使用幼鼠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历的情况下，确定怀孕的激素是否足够，以及产后(孕妇怀孕大鼠在怀孕第20天切除子宫-卵巢切除)是否足够，以及(4)确定怀孕期间何时以及是否出现特殊奖励状态。在目标3中，我们将使用这一独特的行为模型来研究这些奖励过程的神经基础。在雌性的这种特殊奖赏状态中，参与的神经底物将使用三个依赖变量的免疫细胞化学来确定，c-Fos用于确定神经元的一般参与/激活，荷马1a用于确定与谷氨酸相关的激活，CART肽用于确定激活的药理学方面。

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.