The role of human placental transporters in the efflux of bupropion

Abstract

s / Drug and Alcohol Dependence 146 (2015) e34–e117 e65 and Total SS score associated with an estimated 2.0, 2.1, 1.7, 1.7fold greater odds of choosing d-AMPH, respectively. The strongest relationship occurred at the 10mg dose. Among females, SS was not associated with d-AMPH choice. Conclusions: These preliminary results suggest that, even among healthy adults, elevated SS may be associated with increased sensitivity tod-AMPH,particularly amongmalesexposed to a moderate d-AMPH dose. Analyses on the association between SS and subjective response to d-AMPHwill also be presented at the meeting. This study represents the first to investigate the influence of SS on d-AMPH reinforcement using a discrete-trial choice procedure with multiple d-AMPH doses and multiple exposures to each dose. Financial support: R03DA027480 and T32DA007242. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.544 The role of human placental transporters in the efflux of bupropion Svetlana Patrikeeva, Daria Vernikovskaya, Mahmoud S. Ahmed, Gary Hankins, Tatiana Nanovskaya Department of Obstetrics & Gynecology, UTMB, Galveston, TX, United States Aims: The function of human placental efflux transporters is the extrusion of their substrates from the feto-placental unit to the maternal circulation. The aim of this investigation was to identify the placental efflux transporters involved in the extrusion of bupropion. Methods: The expression of efflux proteins in placental apical membraneswas determined byWestern blots. The ATP-dependent uptakeof [3H]-bupropionand [3H]-estrone sulfatewasdetermined using commercially available insideout vesicles (IOV) prepared from Sf9 insect cells transfected with one of the following human efflux transporters;MRP1,MRP2,MRP3, BCRP and P-gp. Bupropion inhibition of the ATP-dependent uptake of the [3H]-estrone sulfate in over-expressed systems and in placental IOVwas utilized to determine the interaction of bupropion with each transporter. Results: Protein expression of the efflux transporters in human placental apical membranes accounted for approximately 20% of the total proteins and was as follows: MRP1, MRP2<MRP3<Pgp<BCRP. The ATP-dependent uptake of [3H]-bupropion and [3H]-estrone sulfate by BCRP, MRP1, and MRP3 expressed vesicles was determined. In the presence of 60ffJM bupropion, the uptake of [3H]-estrone sulfate by BCRP expressed vesicles was inhibited by 90%. Similarly, MRP1 and MRP3 expressed vesicles were inhibited by 50% and 30%, respectively. In addition, 60ffJM of bupropion inhibited the ATPdependent uptake of [3H]-estrone sulfate in placental IOV by 40%. Conclusions: The data strongly suggest that the placental efflux transporters BCRP,MRP1 andMRP3 could be involved in regulating the maternal-to-fetal transfer of bupropion during pregnancy. Financial support: Supported by a NIDA grant RO1DA030998 to TN and GH. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.545 Exploring brain morphology in poly-stimulant abuse: shape, volume, and surface area abnormalities in Ecstasy-cocaineand methamphetamine-preferring individuals Doris Payer1, Min Tae Park1, Stephen Kish1, Jason Lerch2, Isabelle Boileau1,3, M. Mallar Chakravarty1,3 1 Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada 2 Medical Biophysics, University of Toronto, Toronto, ON, Canada 3 Psychiatry, University of Toronto, Toronto, ON,