Extracellular cocaine and dopamine concentrations are linearly related in rat striatum.

Microdialysis and gas chromatography/mass spectrometry were used to determine temporal cocaine concentration profiles in the rat striatum following intraperitoneal (i.p.) cocaine injection. For a 30 mg/kg i.p. dose, cocaine reached a maximum in vivo concentration of 10.1 microM within 30 min, and then rapidly declined. A non-linear fit of a kinetic model to the experimental cocaine data gave a first-order rate constant for the appearance of cocaine in the extracellular fluid of the striatum after a 30 mg/kg dose of cocaine of 0.0304/min and a first-order rate constant of 0.0386/min for the disappearance of cocaine from the extracellular fluid. When combined with previous dopamine results for a 30 mg/kg i.p. cocaine dose, cocaine concentrations were found to be highly correlated (r = 0.963) with dopamine concentrations for the same point in time. The slope was 36.8 nM dopamine/microM cocaine and the y-intercept was 29.9 nM dopamine. Maximum dopamine and maximum cocaine concentrations were also found to be linearly related to i.p. dose of cocaine for doses of 3, 10, and 30 mg/kg.