Disposition of cocaine in blood and brain after a single pretreatment.
In vivo microdialysis studies reveal that repeated cocaine administration will enhance the extracellular level of dopamine that occurs following subsequent challenge injections of cocaine. Not only are dopamine levels enhanced, but the in vivo concentration of cocaine in the brain and blood is also increased as a result of repeated cocaine exposure. Increases in cocaine levels can, in part, account for the behavioral sensitization that occurs as a result of repeated cocaine treatment. The present study reveals that enhanced cocaine concentrations can be observed after a single exposure to cocaine and that enhanced levels are not observed when the challenge injection of cocaine is given by an intravenous as opposed to an intraperitoneal injection. Enhanced cocaine levels were also not due to a decrease in the rate of cocaine metabolism that leads to the formation of benzoylecgonine. Repeated cocaine exposure produces effects that enhance in vivo levels of cocaine and these effects occur outside of blood and brain environments. Pharmacokinetic effects play a major role in the development of cocaine-induced behavioral sensitization.
Pettit
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SRI International, Menlo Park, CA 94025.
Pettit
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D000818:Animals; D001923:Brain Chemistry; D003042:Cocaine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D004361:Drug Tolerance; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D003042:Cocaine