Tsibulsky V L, Norman A B
Division of Neuroscience, Department of Psychiatry, College of Medicine, University of Cincinnati, Cincinnati, OH 45267-0559, USA.
Brain Res. 1999 Aug 21;839(1):85-93. doi: 10.1016/s0006-8993(99)01717-5.
The intervals between self-injections of cocaine by rats are defined by an equation that contains only three parameters: the dose of cocaine administered, the elimination half-life of cocaine, and an amount of cocaine in the body, which we have termed the cocaine satiety threshold. This latter parameter is defined as the maximal level of cocaine at which the probability of self-administration approximates one and above which the probability of self-administration is low. The mathematical model generated mean values for the satiety threshold and the functional elimination half-life of cocaine of approximately 1.7 mg/kg (i.v.) and 8.2 min, respectively. Therefore, the simple equations presented here permit the measurement of the pharmacokinetics and pharmacodynamics of cocaine using self-administration behavior as a bioassay. Our satiety model predicts that when cocaine levels are maintained above the satiety threshold, rats would not self-administer cocaine. The elimination rate of cocaine at the satiety threshold was calculated to be approximately 2 microg kg(-1) s(-1). Therefore, an infusion of cocaine at this rate should maintain cocaine levels fractionally above the satiety threshold. A continuous infusion of cocaine at this rate prevented cocaine self-administration for the duration of the infusion, thereby confirming the validity of the satiety model. These equations provide a quantitative description of cocaine self-administration and contain no subjective terms, implying that concepts such as "craving", drug "wanting" and "liking" and "reinforcement", used in psychologically oriented models, are not necessary for descriptions of this behavior in rats.
给予的可卡因剂量、可卡因的消除半衰期以及体内的可卡因量，我们将其称为可卡因饱腹感阈值。后一个参数被定义为可卡因的最大水平，在该水平下自我给药的概率接近1，高于此水平自我给药的概率则较低。该数学模型得出的饱腹感阈值和可卡因的功能性消除半衰期的平均值分别约为1.7毫克/千克（静脉注射）和8.2分钟。因此，这里给出的简单方程式允许以自我给药行为作为生物测定法来测量可卡因的药代动力学和药效学。我们的饱腹感模型预测，当可卡因水平维持在饱腹感阈值以上时，大鼠不会自行注射可卡因。经计算，在饱腹感阈值时可卡因的消除速率约为2微克·千克-1·秒-1。因此，以该速率输注可卡因应能使可卡因水平略高于饱腹感阈值。以该速率持续输注可卡因在输注期间可防止可卡因的自我给药，从而证实了饱腹感模型的有效性。这些方程式对可卡因的自我给药进行了定量描述，且不包含主观术语，这意味着在以心理学为导向的模型中使用的诸如“渴望”、药物“需求”“喜好”和“强化”等概念，对于描述大鼠的这种行为并非必要。
