Ernest Gallo Clinic and Research Center, University of California at San Francisco, Emeryville, CA 94608,USA.
Neuropsychopharmacology. 2010 Feb;35(3):783-91. doi: 10.1038/npp.2009.187. Epub 2009 Nov 18.
Conditioned responding to drug-predictive discrete cues can be strongly modulated by drug-associated contexts. We tested the hypothesis that differential recruitment of the nucleus accumbens (NAc) core and shell mediates responding to drug cues in a drug vs non-drug context. Rats were trained to discriminate between two 10-s auditory stimuli: one stimulus (CS+) was paired with ethanol (10% v/v; 0.2 ml; oral) whereas the other (CS-) was not. Training occurred in operant conditioning chambers distinguished by contextual stimuli, and resulted in increased entries into the ethanol delivery port during the CS+ when compared with the CS-. In experiment 1, port entries were then extinguished in a second context by withholding ethanol, after which context-induced renewal of ethanol-seeking was tested by presenting both stimuli without ethanol in the previous training context. This manipulation stimulated strong responding to the CS+ in rats pretreated with saline in the core (n=9) or shell (n=10), which was attenuated by pharmacologically inactivating (muscimol/baclofen; 0.1/1.0 mM; 0.3 microl/side) either subregion pretest. In experiment 2, after discrimination, training rats were habituated to a different context in which ethanol and both stimuli were withheld. Cue-induced ethanol-seeking was then elicited by presenting the CS+ and CS- without ethanol in the different context. Saline-pretreated rats responded more to the CS+ than the CS- (core n=8; shell n=9), and inactivating the core but not shell attenuated this effect. These data highlight an important role for the core in cue-induced ethanol-seeking, and suggest that the shell is required to mediate the influence of contexts on conditioned ethanol-seeking.
条件性药物预测离散线索反应可以被药物相关环境强烈调节。我们测试了这样一个假设，即伏隔核（NAc）核心和壳区的差异募集介导了在药物与非药物环境中对药物线索的反应。大鼠被训练区分两种 10 秒的听觉刺激：一种刺激（CS+）与乙醇（10% v/v；0.2ml；口服）配对，而另一种（CS-）则不配对。训练是在操作条件反射室中进行的，通过环境刺激来区分，与 CS-相比，当 CS+出现时，大鼠进入乙醇给药口的次数增加。在实验 1 中，然后在第二个环境中通过停止给予乙醇来消除端口条目，之后通过在以前的训练环境中不给予乙醇来测试环境诱导的乙醇寻求的恢复。这种操作刺激了在核心（n=9）或壳区（n=10）中用生理盐水预处理的大鼠对 CS+的强烈反应，这一反应被预先测试中两种亚区的药理学失活（毒蕈碱/巴氯芬；0.1/1.0mM；0.3 微升/侧）减弱。在实验 2 中，在辨别后，训练大鼠适应于不同的环境，其中乙醇和两种刺激都被停止。然后，在不同的环境中，不给予乙醇的情况下，呈现 CS+和 CS-，从而引发线索诱导的乙醇寻求。用生理盐水预处理的大鼠对 CS+的反应比对 CS-的反应更强（核心 n=8；壳区 n=9），而失活核心但不失活壳区则减弱了这种效应。这些数据突出了核心在线索诱导的乙醇寻求中的重要作用，并表明壳区是介导环境对条件性乙醇寻求影响所必需的。
