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者热衷于通过加强同伴互动、冒险以及增加食物消耗和药物使用来寻求奖励刺激。 青春期的这些行为特征在不同物种中高度保守，前脑区域（例如前额皮质、杏仁核、伏隔核和相关的多巴胺输入）中与青春期相关的转变也与这些行为以及将享乐价值和激励动机归因于自然奖励、滥用药物及其相关线索有关。 一个关键的核心问题仍然存在，限制了对青春期问题行为的理解并试图辨别其神经基础：青少年相关的针对自然奖励和滥用药物的行为的增加是否与他们归因于这些奖励刺激的价值的增加或减少有关？一方面，青少年可能会追求某些自然奖励和药物，因为他们通常对这些刺激表现出（或倾向于发展）强烈的激励动机。 或者，青少年可能会热衷于寻求这些奖励，因为他们试图补偿奖励回路中与年龄相关的不敏感，这种不敏感会产生部分的、发育性表达的快感缺失。 使用已建立的大鼠青春期模型，并关注对青少年特别重要的三种自然奖励：社交互动、新奇事物和食欲刺激，拟议的工作将测试这些可能性并确定这些奖励的神经标记物的年龄特异性表达。 该提案中的工作将回答以下问题：相对于成熟动物，青少年对自然奖励的享乐影响是否减弱（Sp.目标1）？他们是否表现出对自然奖励的激励动机增加（Sp.目标2），或者他们在长期服用药物或压力源后是否异常容易对这些奖励产生激励敏感性（Sp.目标3）？与成熟动物相比，青少年在前额皮质、杏仁核、伏隔核和相关回路中是否表现出独特的区域大脑激活模式，以响应自然奖励及其线索（Sp. Aim 4）？拟议的工作将进一步了解青少年行为方式的原因，确定这些与年龄相关的倾向背后的候选神经区域，并帮助制定治疗表现出药物滥用问题或其他过度奖励导向行为的策略。

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.