Methylphenidate alters NCS-1 expression in rat brain.
Methylphenidate has been used as an effective treatment for attention deficit hyperactivity disorder (ADHD). Methylphenidate (MPH) blocks dopamine and norepinephrine transporters causing an increase in extracellular levels. The use of psychomotor stimulants continues to rise due to both the treatment of ADHD and illicit abuse. Methylphenidate sensitization mechanism has still poor knowledge. Neuronal calcium sensor 1 was identified as a dopaminergic receptor interacting protein. When expressed in mammalian cells, neuronal calcium sensor 1 attenuates dopamine-induced D2 receptor internalization by a mechanism that involves a reduction in D2 receptor phosphorylation. Neuronal calcium sensor 1 appears to play a pivotal role in regulating D2 receptor function, it will be important to determine if there are alterations in neuronal calcium sensor 1 in neuropathologies associated with deregulation in dopaminergic signaling. Then, we investigated if methylphenidate could alter neuronal calcium sensor 1 expression in five brain regions (striatum, hippocampus, prefrontal cortex, cortex and cerebellum) in young and adult rats. These regions were chosen because some are located in brain circuits related with attention deficit hyperactivity disorder. Our results showed changes in neuronal calcium sensor 1 expression in hippocampus, prefrontal cortex and cerebellum mainly in adult rats. The demonstration that methylphenidate induces changes in neuronal calcium sensor 1 levels in rat brain may help to understand sensitization mechanisms as well as methylphenidate therapeutic effects to improve attention deficit hyperactivity disorder symptoms.
Souza
Renan P
RP
Grupo de Pesquisa em Neuropsiquiatria Clínica e Molecular, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil. renanrps@yahoo.com.br
Soares
Eliane C
EC
Rosa
Daniela V F
DV
Souza
Bruno R
BR
Réus
Gislaine Z
GZ
Barichello
Tatiana
T
Gomes
Karin M
KM
Gomez
Marcus V
MV
Quevedo
João
J
Romano-Silva
Marco A
MA
D000375:Aging / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D003720:Densitometry; D004305:Dose-Response Relationship, Drug; D008774:Methylphenidate / Q000494:pharmacology*; D051580:Neuronal Calcium-Sensor Proteins / Q000096:biosynthesis* / Q000235:genetics; D009479:Neuropeptides / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
D000697:Central Nervous System Stimulants; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; C101464:frequenin calcium sensor proteins; D008774:Methylphenidate