Maternal Rat Preferences for Pups Versus Cocaine

这些实验的重点是神经生物学介质的动机，以寻求后代与可卡因在产后期间，一个独特的时期，在生活中的女性，她的后代的生存至关重要。我的临床前模型的首要目标是探索产后雌性大鼠的神经回路和神经化学支持动机反应。我相信这些行为和神经生物学数据将提供有用的信息，概括与人类状况有关的过程。这些实验将使用条件性位置偏好（CPP）作为刺激寻求的量度，因为CPP在动机测试期间不需要刺激的存在，因此可以针对在寻求刺激期间唯一活跃的神经基质。 特定目的揭示神经元及其神经递质的网络，这些神经元及其神经递质对于选择与可卡因相关的环境和与小狗相关的环境是必要的。A.内侧视前区（mPOA）是必要的，以确定选择的环境与可卡因的幼崽在一个双重选择的范例？我将在CPP测试期间使用mPOA的神经解剖学部位特异性和短暂失活（布比卡因局部麻醉剂）进行测试。B。回路的哪些额外组件是必要的，以确定选择的环境与幼犬与可卡因呈现在一个双重选择范例？我将使用A中实验中使用的方法，检验以下假设：腹侧被盖区、中脑核和内侧前额叶皮层对于幼犬或可卡因相关环境中CPP的表现是必要的。C.多巴胺和谷氨酸介导的神经传递在神经回路的关键组成部分中的因果作用是什么？在CPP测试中，我将通过特定部位的插管将多巴胺能或多巴胺能拮抗剂注射到该回路的有限区域。很可能的是，寻求每一个刺激的激励值和选择是建立在一个分布式神经网络中的动机性反应的组成部分，在这个网络中的神经元激活是状态依赖的，产后状态是一个独特的，必须专门研究。我认为，不同的刺激（幼犬与可卡因）可能会招募这个网络的某些组件比其他更强烈，提供了一个可能的机制，解释为什么一个人的属性不同的激励值不同的刺激。在我的研究范式中，探索调节两种特定刺激之间选择的特定回路，可能会揭示这种高度依赖状态且功能不兼容的选择集的神经基质，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.