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The self-administration of WIN 35,428 and cocaine: comparisons of satiety threshold and elimination

The self-administration of WIN 35,428 and cocaine: comparisons of satiety threshold and elimination

  1. staples
    Norman AB, Buesing WR, Norman MK, Tabet MR, Tsibulsky VL. European Journal of Pharmacology. 2004;483(2-3):281-287.

    Abstract
    Rats that self-administered cocaine at unit doses between 0.75 and 12 μmol/kg with mean inter-injection intervals between approximately 2 and 18 min also reliably self-administered the cocaine analogue WIN 35,428 (β-CFT; (−)-3β-(4-fluorophenyl)tropane-2β-carboxylic acid methyl ester) at unit doses between 0.1 and 1.6 μmol/kg with mean intervals between 10 and 116 min. The long inter-injection intervals of WIN 35,428 necessitated sessions of more than 12 h. The inter-injection intervals were regular and proportional to the unit dose, consistent with the satiety threshold model. Analysis of the mean intervals as a function of unit doses generated values for the mean satiety threshold of cocaine and WIN 35,428 of 6.10 and 0.87 μmol/kg, respectively. The mean t1/2 for cocaine and WIN 35,428 were 11.1 and 69.4 min, respectively. The approximately 43-fold lower rate of consumption of WIN 35,428 relative to cocaine was a product of the seven-fold greater pharmacodynamic potency and the six-fold greater pharmacokinetic potency.