Increased Locomotor Activity and Non-Selective Attention and Impaired Learning Ability in SD Rats after Lentiviral Vector-Mediated RNA Interference of Homer 1a in the Brain

Our previous studies found that Homer 1a, a scaffolding protein localized at the post-synaptic density (PSD) of glutamatergic excitatory synapses, is significantly down-regulated in the brain of spontaneous hypertensive rats (SHR), an animal model of attention deficit hyperactivity disorder (ADHD). Furthermore, a first-line treatment drug for ADHD, methylphenidate, can up-regulate the expression of Homer 1a. To investigate the possible role of Homer 1a in the etiology and pathogenesis of ADHD, a lentiviral vector containing miRNA specific for Homer 1a was constructed in this study. Intracerebroventricular injection of this vector into the brain of Sprague Dawley (SD) rats significantly decreased Homer 1a mRNA and protein expression levels. Compared to their negative controls, these rats displayed a range of abnormal behaviors, including increased locomotor activity and non-selective attention and impaired learning ability. Our results indicated that Homer 1a down-regulation results in deficits in control over behavioral output and learning similar to ADHD.