PT545. The Direct Protein-Protein Interaction between Dopamine Transporter and Dopamine D2 Receptor: A Novel Target Site to Modulate Synaptic Dopamine

Objective: In addition to attention deficits and hyperactivity it is common for children with ADHD to display impaired fine and gross motor skills. The spontaneously hypertensive (SH) rat model of ADHD displays impaired motor learning [1]. We used this characteristic to study if the recently described acoustic noise benefit in learning in children with ADHD [2, 3] is also observed in the SH rat model using the Montoya staircase and Rotarod motor learning paradigms. In addition immunohistochemistry was used to assess differences in neuronal activity in animals treated with 75dBA white noise or ambient silence. Methods: Effects of acoustic white noise (75 dBA) compared to ambient silence (45 dBA) on skilled reach and Rotarod running were investigated in male SH and Wistar controls. In parallel experiments the effect of methylphenidate compared to NaCl was investigated using the same motor learning paradigms. Antibodies for Fos B and Ca2+/calmodulin-dependent protein kinase II was used to investigate neuronal activity. Results: We confirm impaired motor learning in the SH rat compared to Wistar controls. Acoustic noise restored motor learning in SH rats learning the Montoya reach test and the rotarod test, but had no influence on learning in Wistar rats. Methylphenidate completely restored rotarod learning and performance but did not improve skilled reach in the SH rat. Conclusion: Our data suggests that the acoustic noise benefit previously reported in children with ADHD is also shared by the SH rat model of ADHD, and the effect is in the same range as that of methylphenidate treatment. Acoustic noise may be useful as an alternative treatment to stimulant medication in the management of ADHD. These results also strengthens the face validity of the SH rat as an animal model of ADHD.