COCAINE DISRUPTION OF MATERNAL BEHAVIOR--RODENT MODELS

显然，不可能严格地证明可卡因改变 大脑机制甚至部分地解释了可卡因中发现的糟糕的养育方式 由于确定可卡因是一种独立的风险， 很快被许多其他风险因素的存在所混淆。 因此 我们建议研究是否有可卡因介导的出轨， 在一个良好表征的实验室模型，大鼠，母性行为， 研究这种影响的神经生物学基础。 具体目标一。 并 可卡因干扰正常母性行为的维持 在老鼠？ 可卡因对母性行为的影响是自然的， 将使用对照给药检查妊娠结局 用的是Alzet微型渗透泵 自从自我注射可卡因以来 在一个暴饮暴食制度已被记录为人类，我们希望检查 自我管理的狂欢制度可能会干扰 母亲的行为比持续的管理更重要， 范例 剂量将在对数数量级的范围内，并保持在 已知可诱发惊厥或严重致畸的剂量。 应该 任何可卡因引起的分娩困难出现，我们将使用剖腹产 分娩幼崽，因为分娩的经验是不需要的， 怀孕引起的母性行为 具体目标二。 可卡因会改变 大脑中的雌激素和垂体后叶素受体是导致 母性行为，这是否是可卡因改变母性行为的基础？ 行为？ 母体反应的中央指挥所是亚群 雌激素和孕酮敏感神经元在视前区的 个脑袋 我们建议，如果可卡因干扰正常发作或 完全显示母性行为，它可能是这样做，通过影响 类固醇激素受体。 我们将记录可卡因 对神经元中类固醇激素受体的影响， 使用抗体定向的免疫细胞化学的母体反应 对抗雌激素和孕酮受体。 没有一个工人 我们对大鼠母性行为的理解的主要架构师 接近这个问题。 我们对这一困难和 复杂的问题是，我们有经验研究母亲的行为， 神经生物学基础。 我们都没有研究过 滥用药物的神经或行为影响的任何方面。 我们寻求 这些资金将我们的研究能力扩展到一个新的领域。

Clearly it is not possible to rigorously prove that cocaine alteration of brain mechanisms even partly underlies poor parenting found in cocaine abusing women since determination that cocaine is an independent risk is quickly confounded by the presence of many other risk factors. Therefore we propose to examine whether there is a cocaine-mediated derailment of maternal behavior in a well characterized laboratory model, the rat, and to examine the neurobiological basis of this affect. Specific Aim I. Does cocaine interfere with the onset of maintenance of normal maternal behavior in the rat? The effect of cocaine on maternal behavior that is the natural outcome of pregnancy will be examined using the controlled administration with an Alzet osmotic minipump. Since the self-administration of cocaine in a binge regime has been documented for humans, we wish to examine the possibility that a self-administered binge regime might interfere with maternal behavior more consequently than does the constant administration paradigm. The dosages will range a log order in magnitude and remain below the doses known to induce convulsions or to be grossly teratogenic. Should any cocaine-induced parturition difficulties arise we will use Caesarean delivery of pups, since the experience of parturition is not required for pregnancy-induced maternal behavior. Specific Aim II. Does cocaine alter the estrogen and progestin receptors in brain regions key to the onset of maternal behavior, and could this underlie cocaine altered maternal behavior? The central command post of the maternal response is the subset of estrogen and progestin sensitive neurons in the preoptic area of the brain. We propose that if cocaine interferes with the normal onset or complete display of maternal behavior it may be doing so by affecting the steroid hormone receptors in these neurons. We will document cocaine effects on steroid hormone receptors in neurons that are key to the maternal response using immunocyto-chemistry with antibodies directed against estrogen and progestin receptors. No workers who have been the principal architects of our understanding of maternal behavior in rats have approached this problem. Our main contribution to this difficult and complex problem is that we have experience examining maternal behavior and its neurobiological basis. Neither of us has had research experience with any aspect of the neural or behavioral effects of drugs of abuse. We seek these funds to expand our research capacity into a new area.