Altarifi Ahmad A, Negus Sidney Stevens
Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 North 12th Street, Richmond, VA 23298, USA.
Behav Pharmacol. 2011 Oct;22(7):663-73. doi: 10.1097/FBP.0b013e32834aff54.
Intracranial self-stimulation (ICSS) is a procedure used to evaluate the abuse liability of drugs. The μ opioid receptor agonist morphine is an acknowledged drug of abuse, and this study examined factors that may influence expression of abuse-related morphine effects on ICSS in rats. Adult male rats were equipped with intracranial electrodes targeting the medial forebrain bundle, and 10 stimulus frequencies (56-158 Hz in 0.05 log increments) were available during each daily session under a continuous reinforcement schedule. The primary dependent variable was the ICSS rate at each frequency. Under baseline conditions, the ICSS rate increased with frequency. After acute morphine (1-10 mg/kg), rate-decreasing effects predominated at early pretreatment times (10-30 min) and rate-increasing effects predominated at later pretreatment times (100-180 min). Acute morphine effects dissipated after 300 min. Repeated morphine (3.2-18 mg/kg/day×7 days at each dose) produced tolerance to rate-decreasing effects, enhanced expression of rate-increasing effects, and enhanced rate dependency of morphine effects. Withdrawal from repeated morphine produced small but significant dose-dependent decreases in ICSS. These results show that the magnitude and valence of morphine effects on rates of ICSS in rats are strongly influenced by morphine dose and pretreatment time, history of morphine exposure, and baseline ICSS rate.
颅内自我刺激（ICSS）是一种用于评估药物滥用可能性的程序。μ阿片受体激动剂吗啡是一种公认的滥用药物，本研究考察了可能影响滥用相关吗啡效应在大鼠ICSS中表达的因素。成年雄性大鼠被植入靶向内侧前脑束的颅内电极，在连续强化程序下，每天的实验过程中有10个刺激频率（56 - 158赫兹，以0.05对数增量递增）可供使用。主要因变量是每个频率下的ICSS速率。在基线条件下，ICSS速率随频率增加。急性注射吗啡（1 - 10毫克/千克）后，在预处理早期（10 - 30分钟）速率降低效应占主导，而在预处理后期（100 - 180分钟）速率增加效应占主导。300分钟后急性吗啡效应消失。重复注射吗啡（3.2 - 18毫克/千克/天，每种剂量注射7天）产生了对速率降低效应的耐受性，增强了速率增加效应的表达，并增强了吗啡效应的速率依赖性。重复注射吗啡后戒断导致ICSS出现小幅度但显著的剂量依赖性降低。这些结果表明，吗啡对大鼠ICSS速率的效应大小和效价受到吗啡剂量、预处理时间、吗啡暴露史以及基线ICSS速率的强烈影响。
