Research

Modeling Neural Injury Effects of Methamphetamine Metabolism by CYP2D6 in HIV

Agency: NIH/NIDA
Agency Award Number: R21DA036423

To understand the mechanisms by which differences in CYP2D6 activity may contribute to meth-related brain dysfunction, we propose to generate a naturalistic in vitro model of neural injury associated with meth exposure in the context of HIV. We will use human mixed neuroglial cultures derived from fetal tissue donation. As such, the cultures can be genotyped. We propose to treat the cultures with meth and HIV, and (1) measure metabolite formation; (2) determine whether CYP2D6 activity / metabolite quantities are related to amount of cellular injury; and (3) examine how these results are affected by exposure of the cultures to clinically relevant CYP2D6 inhibitors (paroxetine and ritonavir).