Stress and methylphenidate treatment, both modulate neuronal activity in an animal model for ADHD

Abstract

Attention-Deficit/Hyperactivity Disorder (ADHD) is a heterogeneous disorder influenced by complex gene-gene as well as gene-environment interactions. It is therefore not surprising that animals with distinctly different neural defects more or less model the behavioral characteristics of this disorder. Dopamine transporter knock-out (DAT-KO) mice display a phenotype typical for ADHD such as hyperactivity, cognitive impairment and paradoxical calming responses to methylphenidate (MPH) treatment. The aims of our study were to explore the effect of MPH treatment on gene expression in this mouse model and whether the co-factor stress provoked by intra-peritoneal drug application influences the results. Our study revealed distinct influences of the DAT genotype, different types of MPH treatment as well as stress resulting from drug application on the expression levels of investigated immediate early genes (IEGs), also shown to be markers for neuronal activity. In general, the co-factor stress induced an increase in IEGs expression comparing to naïve animals that possibly caused masking effects to the MPH treatment. Additionally, chronic MPH treatment compared to acute MPH treatment attenuates IEGs expression. As stress also interacts with MPH influencing different neural networks and transmitter systems in the brain it can be looked upon as an important co-factor not only in the context of treatment response but also in the context of pathophysiological mechanisms.