Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia.
Pharmacol Rev. 2014 Jul;66(3):869-917. doi: 10.1124/pr.112.007419.
Intracranial self-stimulation (ICSS) is a behavioral procedure in which operant responding is maintained by pulses of electrical brain stimulation. In research to study abuse-related drug effects, ICSS relies on electrode placements that target the medial forebrain bundle at the level of the lateral hypothalamus, and experimental sessions manipulate frequency or amplitude of stimulation to engender a wide range of baseline response rates or response probabilities. Under these conditions, drug-induced increases in low rates/probabilities of responding maintained by low frequencies/amplitudes of stimulation are interpreted as an abuse-related effect. Conversely, drug-induced decreases in high rates/probabilities of responding maintained by high frequencies/amplitudes of stimulation can be interpreted as an abuse-limiting effect. Overall abuse potential can be inferred from the relative expression of abuse-related and abuse-limiting effects. The sensitivity and selectivity of ICSS to detect abuse potential of many classes of abused drugs is similar to the sensitivity and selectivity of drug self-administration procedures. Moreover, similar to progressive-ratio drug self-administration procedures, ICSS data can be used to rank the relative abuse potential of different drugs. Strengths of ICSS in comparison with drug self-administration include 1) potential for simultaneous evaluation of both abuse-related and abuse-limiting effects, 2) flexibility for use with various routes of drug administration or drug vehicles, 3) utility for studies in drug-naive subjects as well as in subjects with controlled levels of prior drug exposure, and 4) utility for studies of drug time course. Taken together, these considerations suggest that ICSS can make significant contributions to the practice of abuse potential testing.
颅内自我刺激（ICSS）是一种行为程序，其中操作性反应由电脑刺激脉冲维持。在研究与滥用相关的药物效应的研究中，ICSS 依赖于电极放置，这些电极放置靶向外侧下丘脑水平的内侧前脑束，并且实验会议操纵刺激的频率或幅度，以产生广泛的基线反应率或反应概率。在这些条件下，药物诱导的低频率/幅度刺激维持的低反应率/概率增加被解释为与滥用相关的效应。相反，药物诱导的高频率/幅度刺激维持的高反应率/概率降低可以解释为滥用限制效应。总体滥用潜力可以从与滥用相关的和滥用限制的效应的相对表达推断出来。ICSS 检测许多类滥用药物的滥用潜力的敏感性和选择性与药物自我给药程序的敏感性和选择性相似。此外，与递增比率药物自我给药程序类似，ICSS 数据可用于对不同药物的相对滥用潜力进行排序。与药物自我给药相比，ICSS 的优势包括 1）同时评估与滥用相关的和滥用限制的效应的潜力，2）与各种药物给药途径或药物载体一起使用的灵活性，3）用于研究药物-naive 受试者以及具有受控水平的先前药物暴露的受试者的实用性，以及 4）用于研究药物时间过程的实用性。综上所述，这些考虑表明，ICSS 可以为滥用潜力测试的实践做出重大贡献。
