Satiety threshold: a quantitative model of maintained cocaine self-administration.
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.
Tsibulsky
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VL
Division of Neuroscience, Department of Psychiatry, College of Medicine, University of Cincinnati, Cincinnati, OH 45267-0559, USA.
Norman
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AB
D000818:Animals; D003042:Cocaine / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D007262:Infusions, Intravenous; D008297:Male; D015233:Models, Statistical; D011336:Probability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012528:Satiety Response; D012646:Self Administration
D003042:Cocaine