Adolescence: Natural Incentives, Motivation and Affect

描述（由申请人提供）：人类青少年及其在各种动物模型中的对应物通过增强同伴互动、冒险以及增加食物消费和药物使用来贪婪地寻求有益的刺激。 青春期的这些行为特征在物种间是高度保守的，前脑区域中与青春期相关的转变也是如此（例如，PFC，杏仁核，杏仁核和相关的DA输入）牵连在这些行为中，并归因于享乐价值和激励动机的自然回报，滥用药物，以及它们的相关线索。 一个关键的核心问题仍然存在，限制了对青少年问题行为的理解，并试图辨别其神经基质：与自然奖励和滥用药物相关的行为增加是否与他们归因于这些奖励刺激的价值增加或减少有关？一方面，青少年可能会追求某些自然奖励和药物，因为他们通常表现出（或倾向于发展）强烈的激励动机。 或者，青少年可能会热切地寻求这些奖励，因为他们试图弥补奖励回路中与年龄相关的不敏感性，这种不敏感性产生了部分的，发育性表达的快感缺失。 使用一个已建立的大鼠青春期模型，并专注于对青少年特别重要的三种自然奖励：社会互动，新奇感和食欲（味觉）刺激，拟议的工作将测试这些可能性，并确定这些奖励的神经标志物的年龄特异性表达。 在这项建议的工作将回答以下问题：青少年表现出衰减的享乐影响自然回报相对于成熟的动物（SP。目的1）？他们是否表达了对自然奖励的激励动机（SP目标2），或者他们是否异常倾向于在慢性药物或压力源后对这些奖励产生激励敏感性（SP目标3）？与成年动物相比，青少年是否在PFC、杏仁核、杏仁核和相关回路中表现出独特的区域脑激活模式，以响应自然奖励及其提示（Sp. Aim 4）？拟议的工作将进一步了解为什么青少年的行为方式，确定这些与年龄相关的倾向的候选神经区域，并帮助为治疗表现出药物滥用问题或其他过度奖励导向行为的青少年提供信息。

DESCRIPTION (provided by applicant): Human adolescents and their counterparts in a variety of animal models avidly seek out rewarding stimuli through heightened peer interactions, risk taking, and increases in food consumption and drug use. These behavioral features of adolescence are highly conserved across species, as are adolescence-associated transformations in forebrain regions (e.g., PFC, amygdala, accumbens, and associated DA input) implicated in these behaviors and in attributing hedonic value and incentive motivation to natural rewards, drugs of abuse, and their associated cues. A crucial core question remains, constraining understanding of problem behaviors in adolescence and attempts to discern their neural substrates: Are adolescent-associated increases in behaviors directed towards natural rewards and drugs of abuse related to increases or decreases in the value they attribute to these rewarding stimuli? On the one hand, adolescents might pursue certain natural rewards and drugs because they normally exhibit (or are prone to develop) strong incentive motivation for these stimuli. Alternatively, adolescents may avidly seek these rewards because they are attempting to compensate for an age-related insensitivity in reward circuits that produces a partial, developmentally expressed anhedonia. Using an established model of adolescence in the rat and focusing on three natural rewards of particular significance for adolescents: social interactions, novelty, and appetitive taste) stimuli, the proposed work will test these possibilities and determine age-specific expression of neural markers for these rewards. Work in this proposal will answer the following questions: Do adolescents exhibit attenuated hedonic affect to natural rewards relative to mature animals (Sp. Aim 1)? Do they express increased incentive motivation for natural rewards (Sp. Aim 2) or are they unusually prone to develop incentive sensitization to these rewards following chronic drugs or stressors (Sp. Aim 3)? Do adolescents exhibit unique patterns of regional brain activation in PFC, amygdala, accumbens and related circuitry in response to natural rewards and their cues when compared with mature animals (Sp. Aim 4)? The proposed work will further understanding of why adolescents behave the way they do, identify candidate neural regions underlying these age-related proclivities, and help inform strategies for the treatment of adolescents exhibiting drug abuse problems or other excessive reward-directed behaviors.