In this I/START application from a junior investigator, we propose to use magnetic resonance imaging (MRI) in animals to test the hypothesis that early exposure to methylphenidate (MPH) alters neurobiological development. Stimulants, such as MPH, are the treatment of choice for children with Attention Deficit/Hyperactivity Disorder (ADHD), which is one of the most prevalent childhood disorders and affects an average of 6% of the population. Even though stimulants have been used to treat ADHD since the 1950' s, we know very little about the long-term enduring effects of pharmacotherapy on the developing brain. Research on this topic has become even more imperative, as children are being treated more aggressively and earlier (as young as 2 years of age) with pharmacotherapy for ADHD. From the adult preclinical literature, we know that exposure to stimulants produces enduring changes in the underlying neurobiology and neuroanatomy of the reward systems. In our animal model of childhood exposure to stimulants, we have shown that pre-pubertal exposure to the stimulant MPH produces different - even opposite - enduring changes than post-pubertal exposure (Andersen et al., 2002). This increase in the aversive properties of cocaine following pre-pubertal MPH exposure parallels clinical observations of reduced substance use disorder in adolescents who had received pharmacotherapy for their ADHD (Biederman et al., 1999). Funding from the I/START initiative will enable the PI to expand her basic research interests as a developmental psychopharmacologist to the more clinically relevant domain of neuroimaging. Preliminary MRI data will be collected and analyzed in animals that have been exposed to MPH pre-pubertally for the """"""""proof of concept"""""""" that early medication produces enduring and specific changes in brain activity. These important pilot data will then serve as the basis for an R01 application that will determine the nature and mechanism by which early drug exposure imprints on brain activity in rats and humans.
| Andersen, Susan L; Napierata, Lee; Brenhouse, Heather C et al. (2008) Juvenile methylphenidate modulates reward-related behaviors and cerebral blood flow by decreasing cortical D3 receptors. Eur J Neurosci 27:2962-72 |
| Andersen, Susan L (2005) Stimulants and the developing brain. Trends Pharmacol Sci 26:237-43 |
| Carlezon Jr, William A; Mague, Stephen D; Andersen, Susan L (2003) Enduring behavioral effects of early exposure to methylphenidate in rats. Biol Psychiatry 54:1330-7 |
