Smith Laura N, Penrod Rachel D, Taniguchi Makoto, Cowan Christopher W
Department of Psychiatry, Harvard Medical School, McLean Hospital.
Department of Psychiatry, Harvard Medical School, McLean Hospital;
J Vis Exp. 2016 Feb 18(108):53107. doi: 10.3791/53107.
It is thought that rewarding experiences with drugs create strong contextual associations and encourage repeated intake. In turn, repeated exposures to drugs of abuse make lasting alterations in the brain function of vulnerable individuals, and these persistent alterations likely serve to maintain the maladaptive drug seeking and taking behaviors characteristic of addiction/dependence(2). In rodents, reward experience and contextual associations are frequently measured using the conditioned place preference assay, or CPP, wherein preference for a previously drug-paired context is measured. Behavioral sensitization, on the other hand, is an increase in a drug-induced behavior that develops progressively over repeated exposures. Since sensitized behaviors can often be measured after several months of drug abstinence, depending on the dose and length of initial exposure, they are considered observable correlates of lasting drug-induced plasticity. Researchers have found these assays useful in determining the neurobiological substrates mediating aspects of addiction as well as assessing the potential of different interventions in disrupting these behaviors. This manuscript describes basic, effective protocols for mouse CPP and locomotor behavioral sensitization to cocaine.
人们认为，用药物带来的奖赏体验会产生强烈的情境关联，并促使重复用药。反过来，反复接触滥用药物会使易成瘾个体的大脑功能发生持久改变，而这些持续的改变可能会维持成瘾/依赖所特有的适应不良的觅药和用药行为(2)。在啮齿动物中，奖赏体验和情境关联通常使用条件性位置偏爱试验（CPP）来测量，即测量对先前与药物配对的情境的偏爱。另一方面，行为敏化是指药物诱导的行为在反复接触后逐渐增强。由于敏化行为通常在停药几个月后仍可测量，这取决于初始接触的剂量和时长，因此它们被视为持久的药物诱导可塑性的可观察到的相关指标。研究人员发现，这些试验有助于确定介导成瘾各方面的神经生物学底物，以及评估不同干预措施破坏这些行为的潜力。本手稿描述了小鼠CPP和对可卡因的运动行为敏化的基本有效方案。
