Locomotor effects of a D1R agonist are DARPP-32 dependent in adult but not weanling mice.
Evidence suggests that dopamine regulation of motor activity undergoes postnatal maturation. To examine the role of the dopamine 1 receptor (D1R)/dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) signaling pathway for this maturation, we studied the effects of a D1R agonist on motor activity in weanling and adult wild-type (WT) mice and mice that lack DARPP-32, a key messenger in the D1R signaling pathway. Locomotor activity was not affected by D1R activation in WT weanling mice but was significantly stimulated in WT adult mice. This stimulation was absent in DARPP-32 (-/-) adult mice. In contrast, the inhibitory effects that were observed on rearing activity in WT weanling and adult mice were present in DARPP-32 (-/-) mice. DARPP-32 plays a key role for development of D1R motor stimulatory effects.
Scott
Lena
L
Department of Women and Child Health, Karolinska Institutet, Astrid Lindgren Children's Hospital, Stockholm, Sweden. scott@acc.umu.se
Forssberg
Hans
H
Aperia
Anita
A
Diaz-Heijtz
Rochellys
R
D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D000242:Cyclic AMP / Q000378:metabolism; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism / Q000502:physiology*; D005260:Female; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D015398:Signal Transduction; D013997:Time Factors
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; C497929:Ppp1r1b protein, mouse; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D000242:Cyclic AMP; D010749:Phosphoprotein Phosphatases