Center for Drug and Alcohol Programs, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.
Addict Biol. 2011 Apr;16(2):215-28. doi: 10.1111/j.1369-1600.2010.00262.x. Epub 2010 Nov 4.
Relapse is one of the most problematic aspects in the treatment of alcoholism and is often triggered by alcohol-associated environmental cues. Evidence indicates that glutamate neurotransmission plays a critical role in cue-induced relapse-like behavior, as inhibition of glutamate neurotransmission can prevent reinstatement of alcohol-seeking behavior. However, few studies have examined specific changes in extracellular glutamate levels in discrete brain regions produced by exposure to alcohol-associated cues. The purpose of this study was to use glutamate oxidase (GluOx)-coated biosensors to monitor changes in extracellular glutamate in specific brain regions during cue-induced reinstatement of alcohol-seeking behavior. Male Wistar rats were implanted with indwelling jugular vein catheters and intracerebral guide cannula aimed at the basolateral amygdala (BLA) or nucleus accumbens (NAc) core, and then trained to self-administer alcohol intravenously. A separate group of animals were trained to self-administer food pellets. Each reinforcer was accompanied by the presentation of a light/tone stimulus. Following stabilization of responding for alcohol or food reinforcement, and subsequent extinction training, animals were implanted with pre-calibrated biosensors and then underwent a 1-hour cue-induced reinstatement testing period. As determined by GluOx-coated biosensors, extracellular levels of glutamate were increased in the BLA and NAc core during cue-induced reinstatement of alcohol-seeking behavior. The cumulative change in extracellular glutamate in both regions was significantly greater for cue-induced reinstatement of alcohol-seeking behavior versus that of food-seeking behavior. These results indicate that increases in glutamate transmission in the BLA and NAc core may be a neurochemical substrate of cue-evoked alcohol-seeking behavior.
复发是治疗酗酒过程中最成问题的方面之一，通常是由与酒精相关的环境线索引发的。有证据表明，谷氨酸能神经传递在线索诱发的类似复发行为中起着关键作用，因为抑制谷氨酸能神经传递可以防止酒精寻求行为的复燃。然而，很少有研究检查过暴露于与酒精相关的线索后，特定脑区细胞外谷氨酸水平的具体变化。本研究的目的是使用谷氨酸氧化酶（GluOx）涂层生物传感器监测在与酒精相关线索诱发的酒精寻求行为复燃期间特定脑区细胞外谷氨酸的变化。雄性 Wistar 大鼠被植入留置颈静脉导管和脑内导向套管，目的是针对基底外侧杏仁核（BLA）或伏隔核核心（NAc），然后训练他们进行静脉内自我注射酒精。另一组动物接受了自我注射食物丸的训练。每次强化物都伴随着灯光/声音刺激的呈现。在稳定的酒精或食物强化反应后，以及随后的消退训练后，动物被植入预校准的生物传感器，然后进行 1 小时的线索诱发复燃测试期。通过 GluOx 涂层生物传感器确定，在与酒精相关的线索诱发的寻求行为复燃期间，BLA 和 NAc 核心中的细胞外谷氨酸水平增加。在这两个区域中，细胞外谷氨酸的累积变化在与酒精相关的寻求行为复燃时明显大于与食物相关的寻求行为复燃时。这些结果表明，BLA 和 NAc 核心中谷氨酸传递的增加可能是线索诱发的酒精寻求行为的神经化学基础。
