The Effects of Methamphetamine on Phosphorylation Events in the Prefrontal Cortex of Male and Female C57Bl6/J Mice

Abstract

Methamphetamine (METH) is a psychostimulant drug, which over an extended period of time can cause neurological damage, changes in behavior, and acute toxicity. How METH affects the brain and downstream behavior differs between the sexes. However, there is little research regarding the sex-dependent cell signaling pathways effected by METH. To determine how METH affects cell signaling in the brain, as well as, sex-dependent differences, we initiated a broad scope experimental approach investigating the differences in phosphorylation of proteins within the prefrontal cortex (PFC) of male and female mice following an abuse dosing paradigm of METH. The PFC was analyzed because METH exposure causes dopaminergic activity in this region, leading to neurotoxicity. Using phosphoprotein immunoisolation followed by protein gel electrophoresis and coomassie staining, we will be able to detect differences in the phosphorylation state of proteins such as signaling proteins, receptors, transcription factors, and transport proteins. Side-by-side comparison of the phosphorylation state of proteins in the PFC will indicate differences between saline controls and METH exposed animals, as well as, sex-dependent differences. If a difference exists then further research may identify METH specific pathways and receptors, which could be therapeutically targeted.