Forebrain overexpression of CK1delta leads to down-regulation of dopamine receptors and altered locomotor activity reminiscent of ADHD.

ABSTRACT: Dopamine neurotransmission controls motor and perseverative behavior, is mediated by protein phosphorylation, and may be perturbed in disorders of attention and hyperactivity. To assess the role of casein kinase I (CK1) in the regulation of dopamine signaling, we generated a genetically modified mouse line that overexpresses CK1delta (CK1delta OE) specifically in the forebrain. Overexpression was confirmed both at the mRNA and at the protein levels. Under basal conditions, CK1delta OE mice exhibited horizontal and vertical hyperactivity, reduced anxiety, and nesting behavior deficiencies. The CK1delta OE mice also presented paradoxical responses to dopamine receptor stimulation, showing hypoactivity following injection of d-amphetamine or methylphenidate, indicating that CK1 activity has a

SUBMITTER: Zhou M 

PROVIDER: S-EPMC2840146 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature