Kalinichev Mikhail, White David A, Holtzman Stephen G
Department of Pharmacology, Rollins Research Center, Emory University School of Medicine, 1510 Clifton Road, Suite 5074, Atlanta, GA 30322, USA.
Psychopharmacology (Berl). 2004 Dec;177(1-2):61-7. doi: 10.1007/s00213-004-1990-8. Epub 2004 Aug 13.
Vulnerability for development of substance abuse is often associated with a "sensation-seeking" or "thrill-seeking" phenotype. In an animal model, rats more reactive in a novel environment (high responders, HR) are more sensitive to stimulant/reinforcing effects of amphetamine and are more likely to self-administer this drug, than are less reactive animals (low responders, LR).
We tested whether HR and LR also differ in sensitivity to effects of morphine on locomotor activity.
Male Sprague-Dawley rats were categorized as HR or LR based on motor responses to novelty (sorting day; S). After 1 day (B) of baseline activity measurements, subjects were tested daily after SC injections of either morphine (10 mg/kg) or saline for 7 days and again on day 10. Beginning 5 days later, four daily injections of saline and 1.0-10 mg/kg morphine were tested in all animals.
LR and HR were similar in the onset and overall magnitude of sensitization and tolerance following daily morphine administration. HR were more sensitive than LR to locomotor stimulant effects of acute morphine. However, LR had more robust and persistent context-specific increases in activity due to conditioning than did HR, and expression of sensitization was apparent in all behavioral variables.
These results provide further evidence that phenotypic differences between HR and LR may, in part, be associated with differences in the endogenous opioid systems. Differences in sensitivity to acute versus repeated morphine suggest that at least in relation to opioid drugs, these phenotypes may reflect different aspects of drug vulnerability rather than simply the presence or absence of it.
药物滥用易感性通常与“寻求感觉”或“寻求刺激”的表型相关。在动物模型中，与反应较弱的动物（低反应者，LR）相比，在新环境中反应更强的大鼠（高反应者，HR）对苯丙胺的刺激/强化作用更敏感，且更有可能自我给药。
我们测试了高反应者和低反应者对吗啡对运动活动影响的敏感性是否也存在差异。
根据对新环境的运动反应（分类日；S），将雄性Sprague-Dawley大鼠分为高反应者或低反应者。在进行1天（B）的基线活动测量后，每天对大鼠皮下注射吗啡（10mg/kg）或生理盐水，持续7天，并在第10天再次进行测试。5天后，对所有动物进行4次每日生理盐水注射以及1.0 - 10mg/kg吗啡注射的测试。
每日给予吗啡后，低反应者和高反应者在致敏和耐受的起始及总体程度方面相似。高反应者对急性吗啡的运动兴奋作用比低反应者更敏感。然而，由于条件作用，低反应者的活动在特定环境下有更强且持续的增加，且致敏在所有行为变量中均明显表现。
这些结果进一步证明，高反应者和低反应者之间的表型差异可能部分与内源性阿片系统的差异有关。对急性与重复给予吗啡的敏感性差异表明，至少就阿片类药物而言，这些表型可能反映了药物易感性的不同方面，而非仅仅是有无易感性。
