Dopamine and Exploration in Development

描述（由申请人提供）：哺乳动物新生儿保持接近他们的父母或家庭巢穴的照顾和保护，但随着他们成熟和获得独立，他们必须探索他们的环境，了解其资源和危险。这种从依赖到独立的转变是由断奶期间探索新地方的动机的出现所促进的。这种转变对许多物种的成年独立性至关重要，如果不能完成，可能会导致成年后难以适应不熟悉的环境。事实上，对人类婴儿的研究表明，难以应对父母分离可以预测成人疾病，如广场恐怖症和恐慌症，这些疾病与离开熟悉的地方的过度焦虑有关。探索性动机是向成人独立过渡的一个重要组成部分，而神经激素因素对探索性动机的发展性出现的作用却知之甚少。本研究计划调查这种动机在大鼠中的发展出现。这一建议的核心假设是基于几项发现。首先，对成年大鼠的研究表明，对新地点的行为反应取决于丘脑核（NAc）的多巴胺活性。第二，在出生后的第三周，离开家巢和探索新地方的动机出现了。这个建议的中心假设是，年龄依赖性的增强新奇诱发多巴胺活动促进探索行为在出生后第三周。为了验证这一假设，提出了以下研究：1）确定新的环境是否引起NAc多巴胺活性的年龄依赖性增加; 2）确定探索行为的年龄依赖性变化是否依赖于NAc多巴胺释放。

DESCRIPTION (provided by applicant): Mammalian newborns maintain proximity to their parents or a home nest for care and protection but as they mature and gain independence, they must explore their environment to learn of its resources and dangers. This transition from dependence to independence is facilitated by the emergence of a motive to explore novel places during weaning. This transition is critical to adult independence in many species and a failure to complete it may result in difficulty negotiating unfamiliar environments in adulthood. Indeed, studies of human infants have shown that difficulty coping with parental separation can predict adult disorders like agoraphobia and panic disorder, disorders associated with excessive anxiety about leaving a familiar place. The neurohormonal factors that are responsible for the developmental emergence of the exploratory motive, a critical component of the transition to adult independence, are poorly understood. This research proposal investigates the developmental emergence of this motive in the rat. The central hypothesis of this proposal is based on several findings. First, research in adult rats has shown that behavioral responses to novel places are dependent on nucleus accumbens (NAc) dopamine activity. Second, the motive to leave the home nest and explore novel places emerges during the third postnatal week. The central hypothesis of this proposal is that an age-dependent enhancement of novelty-evoked accumbens dopamine activity facilitates exploratory behavior during the third postnatal week. To test this hypothesis studies are proposed which will 1) determine whether novel contexts evoke an age-dependent increase in NAc dopamine activity and 2) determine whether age-dependent changes in exploratory behavior are dependent on NAc dopamine release.