Hitchcock Leah N, Cunningham Christopher L, Lattal K Matthew
Department of Behavioral Neuroscience, Oregon Health & Science University.
Behav Neurosci. 2014 Apr;128(2):217-27. doi: 10.1037/a0036287.
A pervasive finding in animal models of substance abuse is that associations form quickly between contexts and drugs of abuse, such as cocaine. Studies of conditioned place preference (CPP) demonstrate that animals approach cues previously paired with cocaine. This is a commonly used preparation, but the configuration of the CPP apparatus differs across laboratories. Two common apparatus configurations for CPP are one compartment (in which the animal has access to the entire apparatus and spatial cues are irrelevant) or two compartments (in which access is restricted to one half of the apparatus and spatial cues are relevant). We compared the effects of acquisition and extinction of cocaine-induced CPP as a function of configuration. During CPP acquisition, C57BL/6J mice received cocaine paired with one tactile floor (conditioned stimulus; CS+) and saline paired with the other (CS-). CS+ and CS- trials occurred on alternate days in one of three configurations: one-compartment (exposure to the entire apparatus during CS+ or CS-), two-compartment consistent position (exposure to CS+ or CS- in adjacent, spatially distinct compartments), or two-compartment alternating position (exposure to CS+ or CS- in adjacent compartments that alternated spatial locations across days). A stronger preference for the CS+ floor occurred in two- versus one-compartment groups, with the strongest preference observed when cocaine was paired with alternating chamber positions. In contrast, greater loss of preference occurred after extinction in a one-compartment procedure, regardless of one- or two-compartment acquisition history. These findings suggest that a two-compartment configuration facilitated acquisition but attenuated extinction of a cocaine-induced CPP. The use of different CPP configurations may distinguish the underlying substrates and relevant cues for acquisition and extinction processes in cocaine abuse.
药物滥用动物模型中的一个普遍发现是，环境与滥用药物（如可卡因）之间的关联会迅速形成。条件性位置偏爱（CPP）研究表明，动物会接近先前与可卡因配对的线索。这是一种常用的实验方法，但不同实验室的CPP装置配置有所不同。CPP的两种常见装置配置是一个隔间（动物可以进入整个装置，空间线索无关紧要）或两个隔间（动物只能进入装置的一半，空间线索很重要）。我们比较了可卡因诱导的CPP习得和消退效应与装置配置的关系。在CPP习得过程中，C57BL/6J小鼠接受与一种触觉地板配对的可卡因（条件刺激；CS+）和与另一种触觉地板配对的生理盐水（CS-）。CS+和CS-试验在三种配置之一的隔天进行：一个隔间（在CS+或CS-期间暴露于整个装置）、两个隔间一致位置（在相邻、空间不同的隔间中暴露于CS+或CS-）或两个隔间交替位置（在相邻隔间中暴露于CS+或CS-，隔间的空间位置隔天交替）。与一个隔间组相比，两个隔间组对CS+地板的偏好更强，当可卡因与交替的腔室位置配对时，观察到的偏好最强。相比之下，无论习得时是一个隔间还是两个隔间的经历，在一个隔间程序中消退后，偏好的丧失更大。这些发现表明，两个隔间的配置促进了可卡因诱导的CPP的习得，但减弱了其消退。使用不同的CPP配置可能会区分可卡因滥用中习得和消退过程的潜在基质和相关线索。
