DISTRIBUTION AND CLEARANCE OF COCAINE IN BRAIN IS INFLUENCED BY GENETICS

The purpose of this study was to examine the pharmacokinetics of cocai ne in two inbred mouse strains, C57BL/6 (B6) and DBA/2 (D2). Male and female mice were administered 30 mg kg(-1) cocaine IP and killed after 5, 15, 30, or 60 minutes postinjection. Brains were removed quickly a nd assayed for total brain cocaine concentration. Quantification of co caine was conducted using gas chromatography and mass spectrometry. Th e results of this study revealed a strain difference in total brain co caine kinetics. Specifically, we observed that at 5 min onward, Bt mic e cleared cocaine from the brain with a t(1/2) estimated at 22.3 min, while distribution in D2 mice appeared to be incomplete until 15 min w ith a subsequent t(1/2) estimated at 11.2 min. These results show that despite faster clearance by D2 mice, the prolonged time to distributi on in this strain may help explain why D2 mice show initial greater lo comotor activation by cocaine, compared to B6s. (C) 1998 Elsevier Scie nce Inc.