Cerebral DARPP-32 expression after methylphenidate administration in young and adult rats.
Dopamine may alter the phosphorylation state of DARPP-32 that plays a central role in the dopaminergic neurons biology. Studies have shown that DARPP-32/protein phosphatase 1 cascade is a major target for psychostimulants drugs. Methylphenidate is a psychostimulant that acts blocking the dopamine transporter has been used as an effective treatment for Attention Deficit Hyperactivity Disorder. We investigated if methylphenidate could alter DARPP-32 expression in five brain regions (striatum, hippocampus, prefrontal cortex, cortex and cerebellum) in young and adult rats. Our results showed that methylphenidate treatment is able to alter DARPP-32 expression in rat brain. Acute methylphenidate treatment has reduced hippocampal DARPP-32 protein levels in old rats, while chronic methylphenidate treatment has decreased them in old rat hippocampus and young rat cerebellum. It was found an increased cortical expression after chronic methylphenidate administration in old rats. Our results provide the first experimental demonstration that methylphenidate induces changes in total DARPP-32 expression that are posology- and age-related in some rat brain areas, although further studies are needed to shed more light on the mechanisms behind these findings.
Souza
Renan P
RP
Laboratório de Neurociência, Departamento de Saúde Mental, Faculdade de Medicina da Universidade Federal de Minas Gerais, Av Alfredo Balena, 190, Belo Horizonte, 30130-100 - MG, Brazil.
Soares
Eliane C
EC
Rosa
Daniela V F
DV
Souza
Bruno R
BR
Gomes
Karin M
KM
Valvassori
Samira S
SS
Réus
Gislaine Z
GZ
Inácio
Cecília G
CG
Martins
Márcio R
MR
Gomez
Marcus V
MV
Quevedo
João
J
Romano-Silva
Marco A
MA
D000375:Aging / Q000502:physiology*; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000187:drug effects* / Q000378:metabolism; D004334:Drug Administration Schedule; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008774:Methylphenidate / Q000494:pharmacology*; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000697:Central Nervous System Stimulants; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497930:Ppp1r1b protein, rat; D008774:Methylphenidate; D004298:Dopamine