The effect of vivo‐Morpholinos on Dopamine Receptor 1 (Drd1) and physical activity in mice

Abstract

It is suggested that mice exhibiting low physical activity levels overexpress Drd1 and this may be related to activity. This study aimed to evaluate if vivo‐morpholino (Gene Tools LLC) would knock down Drd1 expression and increase activity. Animal procedures were conducted in conformance with the FASEB Statement of Principles for the use of animals in research and education. Male C3H/HeJ (n=6 control; n=6 morpholino) mice (Jackson Labs) ran on wheels. After one week, the control group received a saline IV injection while the morpholino group received an IV vivo‐morpholino injection (11mg•kg−1) for three days. Four days following injection half of the cohort was sacrificed. Soleus and nucleus accumbens were harvested and analyzed on a western blot. The remaining mice were sacrificed and analyzed one week later. Four days post injection the morpholino group had a significant (p=0.03) knockdown of Drd1 in the soleus. There was no difference in Drd1 expression in the nucleus accumbens (p=0.33) nor was there a difference between the control and morpholino group twelve days post injection (p=0.53). There was no difference in wheel running between the control and morpholino group (p=0.42). The use of vivo‐morpholinos is effective in knocking down Drd1 in muscle but not in the nucleus accumbens potentially due to the blood brain barrier. Furthermore our data suggest that the vivo‐morpholinos gene knock‐down is transient.