The self-administration of WIN 35,428 and cocaine: comparisons of satiety threshold and elimination half-life in rats.
Rats that self-administered cocaine at unit doses between 0.75 and 12 micromol/kg with mean inter-injection intervals between approximately 2 and 18 min also reliably self-administered the cocaine analogue WIN 35,428 (beta-CFT; (-)-3 beta-(4-fluorophenyl)tropane-2 beta-carboxylic acid methyl ester) at unit doses between 0.1 and 1.6 micromol/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 micromol/kg, respectively. The mean t(1/2) 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.
Norman
Andrew B
AB
Department of Psychiatry, Division of Neuroscience, College of Medicine, University of Cincinnati, Cincinnati, OH 45267-0559, USA. andrew.morman@uc.edu
Buesing
William R
WR
Norman
Mantana K
MK
Tabet
Michael R
MR
Tsibulsky
Vladimir L
VL
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012528:Satiety Response / Q000187:drug effects* / Q000502:physiology; D012646:Self Administration
C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine