Laboratory of Neurobiology and Behavior, Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Neurosci Biobehav Rev. 2011 Oct;35(9):2000-8. doi: 10.1016/j.neubiorev.2011.01.003. Epub 2011 Jan 15.
The affective foundations of depression and addictions are discussed from a cross-species - animal to human - perspective of translational psychiatric research. Depression is hypothesized to arise from an evolutionarily conserved mechanism to terminate protracted activation of separation-distress (PANIC/GRIEF) systems of the brain, a shutdown mechanism which may be in part mediated by down-regulation of dopamine based reward-SEEKING resources. This shutdown of the brain's core motivational machinery is organized by shifts in multiple peptide systems, particularly increased dynorphin (kappa opioids). Addictions are conceived to be primarily mediated by obsessive behaviors sustained by reward-SEEKING circuits in the case of psychostimulant abuse, and also powerful consummatory-PLEASURE responses in the case of opioid abuse, which in turn capture SEEKING circuits. Both forms of addiction, as well as others, eventually deplete reward-SEEKING resources, leading to a state of dysphoria which can only temporarily be reversed by drugs of abuse, thereby promoting a negative affect that sustains addictive cycles. In other words, the opponent affective process - the dysphoria of diminished SEEKING resources - that can be aroused by sustained over-arousal of separation-distress (PANIC/GRIEF) as well as direct pharmacological over-stimulation and depletion of SEEKING resources, may be a common denominator for the genesis of both depression and addiction. Envisioning the foundation of such psychiatric problems as being in imbalances of the basic mammalian emotional systems that engender prototype affective states may provide more robust translational research strategies, coordinated with, rather than simply focusing on, the underlying molecular dynamics. Emotional vocalizations might be one of the best ways to monitor the underlying affective dynamics in commonly used rodent models of psychiatric disorders.
从跨物种（从动物到人）的转化精神病学研究视角讨论了抑郁和成瘾的情感基础。抑郁被假设是由于一种进化上保守的机制而产生的，该机制旨在终止大脑分离痛苦（恐慌/悲伤）系统的持续激活，这种关闭机制部分可能是通过下调多巴胺为基础的奖励寻求资源来介导的。大脑核心动机机制的关闭是由多种肽系统的转变组织的，特别是增加的强啡肽（kappa 阿片类）。成瘾被认为主要是由奖励寻求回路的强迫性行为介导的，在精神兴奋剂滥用的情况下，也由强烈的满足性愉悦反应介导，而后者反过来又捕获了寻求回路。这两种形式的成瘾以及其他成瘾形式最终都会耗尽奖励寻求资源，导致一种抑郁状态，这种状态只能通过滥用药物暂时逆转，从而产生一种持续的消极情绪，维持成瘾循环。换句话说，即便是持久的分离痛苦（恐慌/悲伤）过度唤醒以及直接的药物刺激和奖励寻求资源的消耗也能引发的对抗性情感过程——奖励寻求资源减少的抑郁——可能是抑郁和成瘾发生的共同因素。将这些精神疾病的基础设想为引发原型情感状态的基本哺乳动物情感系统的失衡，可能会提供更强大的转化研究策略，与潜在的分子动力学相协调，而不仅仅是简单地关注潜在的分子动力学。情绪发声可能是监测常见的精神障碍啮齿动物模型中潜在情感动态的最佳方法之一。
