Effects of Isolation Rearing on Dopamine Release and Reuptake

描述（由申请人提供）：断奶后的社会隔离养育会产生许多行为的长期变化，包括增加运动新奇反应，增加焦虑样行为和增加乙醇消耗。此外，分离物还表现出多巴胺能活性的变化，包括腹侧被盖多巴胺神经元爆发放电增加，伏隔多巴胺增加，伏隔核和杏仁核多巴胺周转量增加。然而，这些先前的研究是有限的，因为它们没有揭示突触前终末功能的各个方面。快速扫描循环伏安法由于具有较高的时间和空间分辨率，是一种测量突触前功能的有力工具。在本研究中，我们将使用伏安法研究社会隔离和群体饲养动物的摄取率、自身受体敏感性以及乙醇反应性。我们将把重点放在伏隔核和杏仁核基底外侧的功能上，因为这些区域被认为对乙醇的强化特性很重要。

DESCRIPTION (provided by applicant): Postweanling social isolation rearing produces long term changes in many behaviors, including increased locomotor novelty response, increased anxiety-like behavior, and increased ethanol consumption. In addition, isolates also show changes in dopaminergic activity, including increases in ventral tegmental dopamine neuron burst firing, increased accumbal dopamine, and increased dopamine turnover in the accumbens and amygdala. However, these previous studies are limited in that they do not reveal aspects of presynaptic terminal function. Fast scan cyclic voltammetry is a powerful tool for measuring presynaptic function due to its high temporal and spatial resolution. In the present study, we will investigate uptake rates and autoreceptor sensitivity as well as ethanol responsiveness in social isolation and group housing reared animals using voltammetry. We will be focusing on function within the nucleus accumbens and basolateral amygdala, as these areas believed to be important for ethanol's reinforcing properties. PUBLIC HEALTH RELEVANCE: The research proposed in this NRSA is significant as alcohol abuse is a major concern for public health and safety. Indeed, alcohol is reported as one of the most abused substances within the United States, representing ~40% of all admissions to drug abuse treatment facilities (SAMHSA, Treatment Episode Data Set, 2008). Because basic science research of alcohol abuse implements non-human animal models, it is important for translational purposes that these animal models somewhat reflect the disorder. For example, animal models of increased drinking may help elucidate the underlying neuronal substrates/mechanisms behind alcoholism. Rats raised in social isolation are a promising candidate for such a model. Similar to humans, socially isolated rats show increases in anxiety and impulsivity, that seemingly predict alcohol consumption levels. Dopamine's putative role in ethanol reinforcement, make it a prime candidate for studying the neural correlates of alcohol abuse. By studying the dopamine systems of these animals, we may gain important insight into underlying mechanisms that increase an animal's propensity to drink. This research is clinically relevant in that it may help direct the development of new drugs for treating alcoholism.