Wakonigg Gudrun, Sturm Katja, Saria Alois, Zernig Gerald
Division of Neurochemistry, Department of Psychiatry, University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
Psychopharmacology (Berl). 2003 Aug;169(1):52-9. doi: 10.1007/s00213-003-1488-9. Epub 2003 May 21.
The nature of the relationship between the dose of a drug of abuse and its reinforcing effect has come under close scrutiny. It is currently debated if the steep ascending part of the biphasic dose-response curve typically obtained in multiple-dosing lever-press-based operant conditioning procedures represents a satiety-driven, all-or-none response or if the response is gradual and tightly adjusted to the various doses of the reinforcer.
Dose-response relationships of drug reinforcers (remifentanil, alfentanil, morphine, cocaine) as well as a physiological reinforcer, i.e. food (sweetened condensed milk) were investigated in a different operant conditioning paradigm, i.e. a runway procedure.
Administration of the mu opioid receptor agonists remifentanil (0.0032-0.1 mg/kg IV), alfentanil (0.032 mg/kg IV), morphine (0.032-1 mg/kg IV), the psychostimulant cocaine (0.001-0.1 mg/kg IV) or sweetened condensed milk (diluted 1:100-1:3 in water) was made contingent upon alley running for male Sprague-Dawley rats.
All drug reinforcers dose-dependently decreased runtimes and, more importantly, significantly increased the percentage of runs at a certain speed (> or =10 cm/s) from an average 29% to an average 71% (water versus milk, 22% versus 83%).
Both drug- and food reinforcers produced a discontinuous, qualitative change in the rats' operant behavior rather than a simple gradual increase along a continuum, an effect that could be seen clearly only after a histogram analysis of runtime distribution.
滥用药物剂量与其强化作用之间关系的本质受到了密切关注。目前存在争议的是,在基于多剂量杠杆按压的操作性条件反射程序中通常获得的双相剂量反应曲线的陡峭上升部分,是代表饱腹感驱动的全或无反应,还是该反应是渐进的且与强化物的各种剂量紧密相关。
在一种不同的操作性条件反射范式即跑道程序中,研究药物强化物(瑞芬太尼、阿芬太尼、吗啡、可卡因)以及一种生理强化物即食物(甜炼乳)的剂量反应关系。
对于雄性斯普拉格 - 道利大鼠,在其跑完跑道后给予μ阿片受体激动剂瑞芬太尼(0.0032 - 0.1毫克/千克静脉注射)、阿芬太尼(0.032毫克/千克静脉注射)、吗啡(0.032 - 1毫克/千克静脉注射)、精神兴奋剂可卡因(0.001 - 0.1毫克/千克静脉注射)或甜炼乳(用水按1:100 - 1:3稀释)。
所有药物强化物均剂量依赖性地缩短了奔跑时间,更重要的是,显著提高了以一定速度(≥10厘米/秒)奔跑的百分比,从平均29%提高到平均71%(水与牛奶相比,分别为22%与83%)。
药物和食物强化物均使大鼠的操作性行为产生了不连续的、质的变化,而非沿连续体的简单渐进增加,只有在对奔跑时间分布进行直方图分析后才能清楚地看到这种效应。