The effect of methylphenidate treatment on the expression of synaptic vesicle proteins in a mouse model for Attention-Deficit/Hyperactivity Disorder

Mice with a genetic deletion of the dopamine transporter (DAT) demonstrate several key features of Attention-Deficit/Hyperactivity Disorder (ADHD) such as hyperactivity, cognitive impairment and paradoxical calming responses towards methylphenidate (MPH), the most potent drug used to treat ADHD patients. Thus, the DAT knockout (KO) mouse model represents a practical mouse model for ADHD. To achieve a better understanding of processes involved in altered dopaminergic neurotransmission, we carried out gene expression analyses of DAT KO and wild-type (WT) mice by employing quantitative Real time-PCR e.g. on genes involved in neurotransmission like the synaptic proteins synaptotagmin (Syt) 1 and 4 and Syntaxin 1A. We could found significantly reduced Syt 1 and 4 expression in striatum of DAT KO mice. In addition, we focused on the mechanisms underlying the effectiveness of MPH. We investigated expression levels of Syt 1 and 4 and Syntaxin 1A in MPH treated DAT-KO and WT control animals as synaptic proteins have already been shown to be involved in the action of psychostimulants. By the use of an acute, a chronic, and a combined acute and chronic treatment paradigm we could reveal selective and differential effects of MPH on the expression of investigated synaptic proteins in different brain regions. Our data further support the critical role of different synaptic proteins in the adaptive plasticity of dopaminergic circuits – with and without psychostimulant treatment.