The effects of modafinil and atomoxetine on dopamine signaling in the striatal subregions of the rat

Abstract

In an effort to combat diseases and disorders that impede our health, comfort and well-being, an abundance of prescription drugs have emerged in the past 60 years. Many prescription drugs have remarkable efficacy for treating the primary symptoms of these diseases and disorders; however, some drugs carry negative side effects that impose their own adverse symptoms, albeit, often to a lesser degree than the primary symptoms. Thus, one of the main objectives of the pharmaceutical industry is to innovate and develop novel therapeutics, which remediate the primary symptoms of disease and lack undesirable negative side effects. However, in order to develop effective novel therapeutics, a comprehensive understanding of the underlying mechanisms of current drugs is critical. The work within this thesis investigates the mechanisms of two neuroactive drugs, which are commonly prescribed by physicians. Chapter I investigates modafinil (Provigil®), which is therapeutic for sleep and psychiatric disorders, and drug addiction therapy. Chapter II investigates atomoxetine (Strattera®), which is prescribed for attention deficit hyperactivity disorder (ADHD) and possesses limited abuse potential, in contrast to current ADHD medications, Adderall® and Ritalin®, which are addictive.The effects of modafinil and atomoxetine on phasic dopamine signaling were investigated. Phasic dopamine signaling has been identified critical for reward learning and seeking, and is hypothesized to contribute to deficits in ADHD and drug addiction.The results herein suggest that alterations in phasic dopamine signaling are involved in the underlying mechanism of modafinil and atomoxetine action and may ultimately contribute to their therapeutic efficacy.