Determination of microdialysis extraction fraction of cocaine by the no net flux method under high, low, and zero steady-state cocaine concentrations in rats.

Abstract

The effect of different steady-state cocaine concentration maintenance on the microdialysis extraction fraction of cocaine (in situ recovery; Ed) in the medial prefrontal cortex (mPFC) was examined. Male, adult Sprague-Dawley rats anesthetized with chloral hydrate were used. All rats were randomly divided into three groups and were given cocaine i.v. infusion of either 0.6 mg/kg/min (group A), 0.3 mg/kg/min (group B), or 0.0 mg/kg/min (group C). A steady-state cocaine concentration in the blood was obtained for both A and B groups. They were 24.3 +/- 2.3 microM, respectively. We then applied the no net flux microdialysis method to determine the Ed of cocaine in vivo for all three groups. Results revealed that there was no significant difference of Ed under these three different infusion regimens (group A: 16 +/- 2%; group B: 17 +/- 1%; group C: 21 +/- 2%). The steady-state cocaine concentration in the mPFC was also estimated to be 17.7 +/- 1.3 microM, 11.3 +/- 2.0 microM, and 0.7 +/- 0.6 microM, respectively. We then concluded that the Ed of cocaine in the mPFC is invariable while the steady-state cocaine concentration in the mPFC was ranging from 0 to 18 microM. This information is useful in the cocaine pharmacokinetic study since scientists are concerned about the variations of Ed while cocaine concentration in the mPFC is changing.