Adolescence: Natural Incentives, Motivation and Affect

描述（由申请人提供）：在各种动物模型中，人类青少年和他们的同龄人通过加强同伴互动、冒险、增加食物消费和药物使用，热切地寻求奖励刺激。青春期的这些行为特征在不同物种中是高度保守的，就像青春期相关的前脑区域（如PFC、杏仁核、伏核和相关的DA输入）的转换一样，这些转换涉及这些行为，并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。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质：青春期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的奖励和药物，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。另外，青少年可能会急切地寻求这些奖励，因为他们试图弥补与年龄相关的奖励回路的不敏感，这种不敏感会产生部分的、发育表达的快感缺乏。利用已建立的大鼠青春期模型，并关注对青少年具有特殊意义的三种自然奖励（社会互动、新奇和食欲味觉刺激），提出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。本提案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. Aim 1）？他们是否对自然奖励表现出更高的激励动机（目标2），或者他们是否异常倾向于在慢性药物或压力刺激后对这些奖励产生激励敏化（目标3）？与成熟动物相比，青少年是否表现出独特的PFC、杏仁核、伏隔核和相关回路的区域大脑激活模式，以响应自然奖励及其提示（Sp. Aim 4）？所提出的工作将进一步理解为什么青少年的行为方式，确定潜在的这些与年龄相关的倾向的神经区域，并帮助制定治疗青少年滥用药物问题或其他过度奖励行为的策略。

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.