Disruption of reelin signaling attenuates methamphetamine-induced hyperlocomotion.
To clarify whether reelin signaling is involved in dopaminergic neurotransmission in the adult mouse brain, we investigated dopamine function in mice lacking reelin (reeler). We found that methamphetamine-induced locomotor activity is significantly attenuated in reeler mice. To elucidate the mechanism of this phenomenon, we first investigated presynaptic dopamine release; however, there were no significant differences in wildtype, heterozygous reeler and homozygous reeler mice. Next, we examined the locomotor response to intra-accumbens injection of dopamine D1 and D2 receptor agonists, and found that lack of reelin signaling results in decreases in both D1 and D2 receptor-mediated dopaminergic functions. In addition, we measured dopamine receptor binding in the striatum, and found that both D1 and D2 classes of dopamine receptors are reduced in reeler mice. Furthermore, we found that the phosphorylation levels of DARPP-32 are also changed by lack of reelin signaling. Finally, to distinguish between a developmental role of reelin or an acute role of reelin in adult mouse, we intraventricularly infused CR-50, a monoclonal antibody against reelin. Interestingly, infusion of CR-50 also significantly reduced methamphetamine-induced hyperlocomotion in wildtype mice, showing that reelin has an acute role in the dopaminergic system. These results indicate that reelin signaling plays a pivotal role in the dopaminergic system in adult mice, especially in postsynaptic levels.
Matsuzaki
Hideo
H
Department of Anatomy and Neuroscience, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Minabe
Yoshio
Y
Nakamura
Kazuhiko
K
Suzuki
Katsuaki
K
Iwata
Yasuhide
Y
Sekine
Yoshimoto
Y
Tsuchiya
Kenji J
KJ
Sugihara
Genichi
G
Suda
Shiro
S
Takei
Nori
N
Nakahara
Daiichiro
D
Hashimoto
Kenji
K
Nairn
Angus C
AC
Mori
Norio
N
Sato
Kohji
K
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001522:Behavior, Animal; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency / Q000276:immunology / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins / Q000172:deficiency / Q000276:immunology / Q000502:physiology*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008818:Mice, Neurologic Mutants; D017551:Microdialysis / Q000379:methods; D009043:Motor Activity / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000276:immunology / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation; D011869:Radioligand Assay / Q000379:methods; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000172:deficiency / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013912:Threonine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015816:Cell Adhesion Molecules, Neuronal; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; C497929:Ppp1r1b protein, mouse; D000091042:Reelin Protein; D013912:Threonine; D008694:Methamphetamine; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases