Differential behavioral phenotypes of dopamine D1 receptor knockdown mice at the embryonic, postnatal, and adult stages

• Published in: International journal of developmental neuroscience 2018-05, Vol.66 (1), p.1-8
• Main Authors: Okubo, Tadashi, Sato, Asako, Okamoto, Hirotsugu, Sato, Toshiya, Sasaoka, Toshikuni
• Format: Article
• Language: English
• Subjects: Age Factors; Aging; Animals; Animals, Newborn; Anti-Bacterial Agents - pharmacology; Conditional knockdown; Corpus Striatum - embryology; Corpus Striatum - growth & development; Corpus Striatum - metabolism; Dopamine and cAMP-Regulated Phosphoprotein 32 - metabolism; Dopamine D1 receptor; Doxycycline - pharmacology; Embryo, Mammalian; Exploratory Behavior - physiology; Gene Expression Regulation, Developmental - drug effects; Gene Expression Regulation, Developmental - genetics; Hyperkinesis - genetics; Hyperkinesis - physiopathology; Locomotion - drug effects; Locomotion - genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor function; Motor Skills - physiology; Postnatal stage; Receptors, Dopamine D1 - deficiency; Receptors, Dopamine D1 - genetics
• ISSN: 0736-5748; 1873-474X
• DOI: 10.1016/j.ijdevneu.2017.11.004

•Conditional D1R knockdown reveals the role of dopamine at various stages.•Motor phenotype of postnatal D1R knockdown is distinct from that of conventional D1R knockout.•D1R has versatile functions at the embryonic, postnatal, and adult stage. Dopamine is widely involved in behaviors related to motor activity, cognition, motivation, and reward. Dopamine signal is transduced through the dopamine receptor gene family. The dopamine D1 receptor (D1R) is highly expressed in the striatum, and is responsible for regulating the motor function. Recently, we have reported that the knockdown (KD) mice in which D1R was conditionally eliminated at adult stage, displayed a hypoactivity in the home cage than wild type mice; however, conventional D1R knockout (KO) mice show hyperactive phenotypes. In order to assess whether the difference in the time of eliminating D1R expression affects the behavioral phenotypes, we generated D1R KD mice at the postnatal and adult stages, and compared their motor function with D1R KO mice. Consequently, D1R KD at postnatal and adult stages resulted in severe locomotive defects compared with D1R KO mice. These results suggested that D1R has versatile functions, and the knockdown timing greatly influences the normal motor activity in the adolescent to adult stages.