Gene Expression Controlling Synaptic Plasticity Following Adolescent Exposure to ADHD-Medications in a Murine Model

Abstract

The abuse, over-prescription, and availability of ADHD psychostimulant medications are increasing in adolescent populations. Our lab previously demonstrated that adolescent mice exposed to ADHD medications, amphetamine (AMPH) and methylphenidate (MPD), demonstrated sex-specific behavioral alterations that persisted into adulthood. Non-ADHD mice exposed to either drug in adolescence exhibited cross-sensitization to a sub-acute methamphetamine dose in adulthood, which implies drug-induced, heightened addiction susceptibility for these animals and associated neural plasticity in the psychomotor and reward pathways. AMPH exposure produced a male-specific sensitizing effect while MPD exposure produced a female-specific effect. This study investigates the mechanism of these behavioral changes by analyzing the regulation of genes during a key developmental window. Adolescent male and female mice were treated with 1-mg/kg AMPH, MPD, or an equal volume of saline for 10 days to model chronic abuse during early adolescence. RNA was isolated from striatum and prefrontal cortex brain regions. Quantitative RT-PCR was used to run 48 PCR array plates, each consisting of 84 genes of interest and controls. Data analysis is currently underway to identify genes expression changes thought to underlie the noted behavioral alterations following adolescent exposure to ADHD medications. Individual gene expression changes will be analyzed by drug and sex. Analysis of thematic groups of genes will also be analyzed using multivariate approaches. An understanding of drug-induced genetic alterations during development and associated susceptibility to addiction will better inform clinical practice and treatment strategies in both adolescent and adult populations.