The Effects of Chronic Adolescent Methylphenidate Abuse on Brain Derived Neurotrophic Factor (BDNF) Expression

Abstract

Methylphenidate (MPD), the active ingredient in Ritalin®, is a prescription psychostimulant whose nootropic effects are used to assist individuals with Attention Deficit Hyperactivity Disorder (ADHD) but is often abused by college students who do not have ADHD. Chronic drug abuse is known to have long lasting effects on neural plasticity as corroborated by previous published data from our lab showing cross-sensitization to amphetamine in female mice treated with methylphenidate using an adolescent dosing paradigm – results demonstrating alterations in neuronal circuitry that persist into adulthood. Brain derived neurotrophic factor (BDNF), a nerve growth factor that aids in supporting neuron survival, growth and differentiation of new neurons, is suspected to play a role in facilitating the changes in neural plasticity induced by chronic drug abuse. For this study, we used the same dosing paradigm, microdissected and homogenized the prefrontal cortex and striatum of each mouse, and isolated total RNA. MPD-induced changes in the expression of BDNF were measured with Quantitative PCR using experimental and internal controls (18s). In the striatum, we observed a three-fold increase in BDNF expression in the males and a three-fold decrease in BDNF expression in the females. The change in BDNF expression and the sex effect observed indicates the nerve growth factor is indeed an integral part of the physical mechanism by which chronic MPD abuse facilitates addiction.