Maternal Rat Preferences for Pups Versus Cocaine

这些实验的重点是产后期与可卡因相比，寻找后代的动机的神经生物学媒介，产后期是雌性生命中的一个独特时期，对其后代的生存至关重要。我的临床前模型的首要目标是探索支持产后雌性大鼠动机反应的神经回路和神经化学。我假设，这些行为和神经生物学数据将提供有用的信息，概括出与人类状况相关的过程。这些实验将使用条件性位置偏好(CPP)作为刺激寻求的衡量标准，因为CPP在动机测试过程中不需要刺激的存在，因此可以针对仅在刺激寻求期间激活的神经底物。 具体目的是揭示选择幼崽相关环境和可卡因相关环境所需的神经元网络及其神经递质。在双重选择范式中，内侧视前区(MPOA)对于决定与幼鼠和可卡因相关的环境的选择是否必要？在CPP测试期间，我将使用神经解剖部位特异性的mPOA暂时失活(使用局部麻醉剂布比卡因)来测试这一点。B.在双重选择范式中，决定与幼崽和可卡因相关的环境选择时，电路的哪些额外组件是必要的？我将使用A中实验中使用的方法，检验腹侧被盖区、伏隔核和内侧前额叶皮质对于幼鼠或可卡因相关环境中的CPP的出现是必要的假设。多巴胺和谷氨酸介导的神经传递在神经回路的关键部件中的因果作用是什么，对于选择与幼崽和可卡因相关的环境是必要的？在CPP测试中，我将通过定点定向插管将多巴胺或谷氨酸能拮抗剂注射到这个回路的有限区域。寻找每个个体刺激的激励价值和选择很可能是在一个分布式神经网络中建立的，该网络是激励反应的组成部分，该网络中的神经元激活是状态依赖的，产后状态是唯一的，必须进行特定的研究。我假设，不同的刺激(幼崽和可卡因)可能会比其他刺激更强烈地招募这个网络的某些组成部分，这提供了一种可能的机制，解释了为什么个人将不同的激励价值归因于不同的刺激。在我的研究范式中，探索在两种特定刺激之间进行选择的特定电路，可能会揭示这种高度状态依赖和功能不相容的选择集所特有的神经基础，寻找和照顾后代或寻找可卡因。

These experiments focus on the neurobiological mediators of motivation to seek offspring versus cocaine during the postpartum period, a unique period in the life of the female, critical for the survival of her offspring. A foremost goal of my preclinical model is to explore the neural circuitry and neurochemistry supporting motivational responses in the postpartum female rat. I posit that these behavioral and neurobiological data will provide information that usefully generalizes to processes related to the human condition. These experiments will use conditioned place preference (CPP) as a measure of stimulus seeking because CPP does not require the presence of the stimulus during motivation testing, so the neural substrates active exclusively during seeking of the stimulus can be targeted. Specific Aim Revealing the network of neurons and their neurotransmitters necessary for the choice of pup-associated versus cocaine-associated environments. A. Is the medial preoptic area (mPOA) necessary to determining the choice of environments associated with pups versus cocaine presented in a dual choice paradigm? I will test this using neuroanatomical site specific and transient inactivation (with bupivacaine a local anesthetic) of the mPOA during CPP test. B. Which additional components of the circuit are necessary to determining the choice of environments associated with pups versus cocaine presented in a dual choice paradigm? I will using methods used in the experiments in A, test the hypothesis that the ventral tegmental area, nucleus accumbens and the medial prefrontal cortex are necessary to the manifestation of CPP for either pup or cocaine-associated environments. C. What is the causal contribution of dopamine and glutamate mediated neurotransmission within key components of the neural circuit necessary for the choice of environments associated with pups versus cocaine? I will inject dopaminergic or glutametergic antagonists via site specifically directed cannulae into limited regions of this circuit at CPP test. It is likely that the incentive value and choice to seek each individual stimulus is established in a distributed neural network that underlies the components of motivated response, and that neuronal activation in this network is state-dependent, and that the postpartum state is a unique one that must be studied specifically. I posit that the different stimuli (pups versus cocaine) may recruit certain components of this network more strongly than others, providing a likely mechanism explaining why an individual attributes different incentive values to different stimuli. Exploring the specific circuitry mediating the choice between the two particular stimuli in my paradigm is likely to reveal neural substrate particular to this highly state dependent and functionally incompatible set of choices, seeking and caring for offspring or seeking cocaine.