Adolescence: Natural Incentives, Motivation and Affect

描述(由申请者提供)：人类青少年和他们在各种动物模型中的同龄人热衷于通过加强同伴互动、冒险以及增加食物消费和药物使用来寻找奖励刺激。青春期的这些行为特征在不同物种之间高度保守，前脑区域(如PFC、杏仁核、伏隔核和相关的DA输入)中与青春期相关的转化也是如此，这些行为和将享乐主义价值和激励归因于自然奖励、滥用药物及其相关线索。一个关键的核心问题仍然存在，这限制了人们对青春期问题行为的理解，并试图辨别他们的神经基础：青春期与自然奖励和滥用药物相关的行为增加是否与他们对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(或倾向于形成)强烈的激励动机。或者，青少年可能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，这会产生部分的、发育性的快感缺乏。利用已建立的大鼠青春期模型，并将重点放在对青少年具有特殊意义的三种自然奖励上：社会互动、新鲜感和食欲刺激，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的年龄特定表达。这项提案中的工作将回答以下问题：相对于成熟的动物，青少年对自然奖励是否表现出减弱的享乐影响(Sp。目标1)？他们是否对自然奖励表现出更强的激励动机(Sp.目标2)还是他们在慢性药物或应激源后异常容易对这些奖励产生激励敏感化(SP。目标3)？与成熟动物相比，青少年在PFC、杏仁核、伏隔核和相关回路中是否表现出独特的大脑区域激活模式，以响应自然奖励及其提示(Sp。目标4)？拟议的工作将进一步了解青少年为什么会这样做，确定这些与年龄相关的倾向背后的候选神经区域，并有助于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.